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Major Depressive disorder

Updated : September 12, 2023





Background

Major Depressive Disorder is a widespread and incapacitating mental health disorder that impacts countless people around the globe. It transcends age, gender, and cultural boundaries, making it one of the most prevalent psychiatric disorders. Major Depressive Disorder often experience a range of symptoms, including changes in sleep patterns, appetite, energy levels, and concentration, which can interfere with their daily functioning.

This disorder casts a long and looming shadow over the lives of those who grapple with it, influencing their emotional well-being, physical health, relationships, and overall quality of life.

Epidemiology

Prevalence:

The lifetime prevalence of MDD is 5-17%

Average prevalence rate is 12 %.

Age of Onset:

MDD can affect individuals of all ages, but the typical age of onset is in late adolescence to early adulthood.

Gender Differences:

Women are about twice as likely as men to be diagnosed with MDD.

Biological, hormonal, and sociocultural factors may influence gender differences in MDD.

Socioeconomic Factors:

Socioeconomic status can impact the risk of MDD.

People from lower socioeconomic backgrounds may have a higher risk due to factors like limited access to healthcare, stressors, and socioeconomic disparities.

Geographic Variations:

The prevalence and incidence of MDD can vary significantly between countries and regions.

Factors like cultural norms, healthcare access, and socioeconomic conditions contribute to these variations.

Risk Factors:

Risk factors including genetics, family history, traumatic life events, chronic stress, and personality traits.

Anatomy

Pathophysiology

Neurochemical Imbalances:

Dysregulation of neurotransmitters: One of the leading theories in depression’s pathophysiology is the dysregulation of neurotransmitters, particularly serotonin, norepinephrine, and dopamine. Reduced levels of these neurotransmitters in certain brain regions can lead to mood disturbances and depressive symptoms.

Neuroendocrine Dysregulation:

Hypothalamic-Pituitary-Adrenal (HPA) Axis: The dysregulation of the HPA axis can lead to an overproduction of stress hormones, including cortisol. Persistent exposure to heightened cortisol levels can bring about alterations in both mood and cognitive functioning, potentially playing a role in the onset of depression.

Inflammatory Processes:

There is growing evidence of a link between inflammation and depression. Chronic inflammation, often indicated by elevated levels of inflammatory markers like cytokines, may contribute to depressive symptoms. Inflammatory processes can affect neurotransmitter metabolism and neural plasticity.

Genetic Factors:

Family and twin research indicate an inherited inclination toward depression, with a genetic component playing a role. It is widely accepted that multiple genes contribute to an individual’s susceptibility to depression, and each gene is thought to exert a modest influence. However, the specific genes responsible for this predisposition are still the subject of ongoing research.

Environmental Factors:

Stressful life events: Traumatic or highly stressful life events, especially during childhood or early adulthood, can increase the risk of developing depression.

Etiology

Biological Factors:

Neurotransmitter Imbalance: One of the most well-established biological factors is the imbalance of certain neurotransmitters in the brain, neurotransmitters like dopamine, serotonin and norepinephrine are pivotal in the regulation of mood. Imbalances in these neurotransmitter levels have been linked to the manifestation of depressive symptoms.

Genetic Factors:

Evidence suggests that a family history of depression can increase an individual’s risk of developing MDD. Genetic studies have identified specific gene variations that may predispose some to depression.

Psychological Factors:

Cognitive Factors: Negative thought patterns, cognitive biases, and distorted thinking can contribute to the onset and persistence of depressive symptoms. This is often a focus of cognitive-behavioral therapy (CBT), a common treatment for MDD.

Environmental Factors:

Stressful Life Events: Traumatic experiences, chronic stress, loss of a loved one, financial difficulties, or major life changes can trigger or exacerbate depressive episodes in susceptible individuals.

Childhood Adversity: Experiences of abuse, neglect, or other adverse childhood events can increase the risk of developing MDD later in life.

Genetics

Prognostic Factors

Psychosocial Factors: Social support, stressors, and life events can impact the prognosis of MDD. Positive social support can enhance recovery, while ongoing stressors can worsen symptoms.

Suicidal Ideation: The presence of suicidal thoughts or behaviors is a serious concern in MDD and can impact prognosis. Individuals with a history of suicide attempts or persistent suicidal ideation may have a higher risk of recurrent episodes and a more complex course.

Cognitive Functioning: Impairments in cognitive functioning, such as difficulties with concentration and memory, can affect prognosis and functional outcomes.

Substance Use: Substance abuse or dependence can complicate the course of MDD and is associated with a less favorable prognosis.

Clinical History

Age group:

Children and Adolescents: MDD can occur in children and teenagers. It’s often characterized by symptoms like irritability, social withdrawal, changes in appetite, and academic decline.

Adults: MDD is most diagnosed in adults. It can affect individuals throughout their adult life, from early adulthood to late adulthood.

Elderly: Depression can also affect older adults. In this age group, it might be associated with factors like chronic illness, loss of loved ones, and social isolation.

Across the Lifespan: MDD can affect people at any age, and its presentation may vary depending on the individual’s developmental stage and life circumstances.

Physical Examination

Vital Signs:

Measure the patient’s blood pressure, pulse rate, respiratory rate, and body temperature.

Neurological Examination:

Evaluate coordination, reflexes, muscle strength, and sensation.

Assess for any neurological deficits that could indicate other medical conditions.

Gastrointestinal System:

Inquire about appetite and weight changes, as significant alterations may be indicative of an underlying medical condition.

Medication and Substance Use:

Ask about current medications, including over the counter and herbal supplements, as well as any substance use, including alcohol and illicit drugs, which can influence mood.

Sleep Patterns:

Discuss the patient’s sleep habits and any sleep disturbances, as sleep problems often co-occur with depression.

Age group

Associated comorbidity

Anxiety Disorders: Major Depressive Disorder frequently occurs alongside various anxiety disorders. The shared symptoms of depression and anxiety can result in a more complex clinical manifestation.

Substance Abuse: People experiencing Major Depressive Disorder may resort to alcohol or drug usage as a means of dealing with the challenges posed by their depressive symptoms. This can lead to substance use disorders, making it essential to address both conditions simultaneously.

Suicidal Thoughts or Behaviors: Severe depression can increase the risk of suicidal ideation and self-harm. It’s crucial for individuals with MDD to seek help and support from mental health professionals if they experience these thoughts or behaviors.

Eating Disorders: Conditions like anorexia nervosa, bulimia nervosa, or binge-eating disorder may co-occur with MDD. These disorders often involve distorted body image and unhealthy relationships with food.

Chronic Pain: Depression and chronic pain frequently coexist. Chronic pain conditions like fibromyalgia or arthritis can contribute to the development or exacerbation of MDD, & Depression has the potential to amplify the experience of pain.

Sleep Disturbances: Many individuals with MDD experience disrupted sleep patterns, such as insomnia or hypersomnia (excessive sleep). These disturbances can worsen depressive symptoms and vice versa.

Social Isolation: Depression often leads to social withdrawal and isolation. Isolation and an absence of a strong social network can enhance the endurance of depressive manifestations and enhance sentiments of hopelessness.

Cognitive Impairment: Depression can affect cognitive functions such as memory, attention, and decision-making. This can impact a person’s ability to work or perform daily activities.

Reduced Physical Activity: People who have Major Depressive Disorder (MDD) may experience a decrease in their physical activity levels, potentially resulting in the adoption of a sedentary way of life. Lack of exercise can worsen both physical and mental health.

Negative Impact on Relationships: Depression can strain relationships with family and friends. The withdrawal, irritability, and sadness associated with depression can make it challenging to maintain healthy social connections.

Poor Academic or Occupational Performance: Depression can lead to decreased concentration and motivation, which can affect academic and occupational performance. This can result in decreased productivity and satisfaction in these areas.

Associated activity

Acuity of presentation

Acute Onset: Some individuals may experience a sudden and acute onset of MDD symptoms. They might go from feeling relatively fine to severely depressed within a short period. A significant life event, trauma, or stressor can trigger this.

Chronic or Persistent: In other cases, the acuity may be less pronounced, and the symptoms may develop gradually over time. These individuals may have a long history of low-level depressive symptoms that have gradually worsened, leading to the diagnosis of MDD.

Severe Symptoms: Acuity can also be reflected in the severity of symptoms. Some individuals may experience very severe symptoms, including intense feelings of despair, suicidal thoughts, and physical symptoms like significant changes in weight or sleep patterns.

Moderate Symptoms: Others may have a more moderate presentation, with symptoms that interfere with daily life but are not as severe. They may still experience significant distress and impairment in functioning but not to the same extent as those with severe symptoms.

Atypical Features: Some individuals may present with atypical features of MDD, such as increased sleep, increased appetite, and leaden paralysis. These atypical symptoms can impact the acuity of the presentation and make it challenging to diagnose.

Recurrent Episodes: For some, MDD may be recurrent, with episodes of acute symptoms separated by periods of remission. The acuity can vary from episode to episode, with some being more severe than others.

Differential Diagnoses

Bipolar Disorder: Periods of sadness (like MDD) alternate with periods of mania or hypomania in bipolar disorder. Distinguishing between MDD and bipolar disorder can be challenging due to overlapping depressive symptoms.

Persistent Depressive Disorder (Dysthymia): Dysthymia is a chronic form of depression characterized by milder, but long-lasting depressive symptoms. It may be considered when symptoms persist for at least two years.

Adjustment Disorder with Depressed Mood: This condition occurs in response to a specific stressor or life event and leads to symptoms of depression. It is typically time-limited and resolves when the stressor is removed.

Post-Traumatic Stress Disorder (PTSD): PTSD can include symptoms such as persistent negative mood, emotional numbing, and loss of interest in activities, which may overlap with depressive symptoms.

Substance-Induced Mood Disorder: Substance abuse or withdrawal from certain substances (e.g., alcohol, drugs) can mimic the symptoms of depression. A thorough history of substance use is essential in the evaluation.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Initial Assessment and Diagnosis:

Comprehensive evaluation conducted by a certified mental health expert for the purpose of diagnosing Major Depressive Disorder (MDD) and eliminating the possibility of other concurrent medical or psychiatric disorders.

Psychoeducation:

Educating the patient and their family about depression, its symptoms, and the treatment options available.

Psychotherapy:

Cognitive-Behavioral Therapy (CBT): A systematic and purpose-driven strategy designed to assist individuals in recognizing and modifying detrimental thought patterns and behaviors that are exacerbating their depression.

Psychodynamic Therapy: Exploring unconscious conflicts and past experiences that may be contributing to depression.

Behavioral Activation: Encouraging engagement in rewarding activities to counteract the withdrawal and isolation often associated with depression.

Mindfulness-Based Cognitive Therapy (MBCT): Combining mindfulness techniques with CBT to prevent depressive relapse.

Pharmacotherapy:

Antidepressant Medications: Depending on the severity and type of depression, antidepressant medications such as SSRIs, SNRIs and Norepinephrine Reuptake Inhibitors, or other classes of drugs may be prescribed. It’s crucial to monitor for side effects and therapeutic response.

Adjunctive Medications: In some cases, other medications like mood stabilizers or atypical antipsychotics may be added to the treatment regimen, especially when there are symptoms of anxiety or mood instability.

Medication management should involve close monitoring by a psychiatrist, including regular assessments of medication effectiveness and potential side effects.

Electroconvulsive Therapy (ECT):

ECT may be considered when depression is severe, treatment-resistant, or when rapid symptom relief is essential. It’s typically administered under general anesthesia by a specialized team.

Lifestyle Modifications:

Promoting patients to embrace a wholesome way of life, encompassing routine physical activity, a well-rounded nutritional regimen, sufficient rest, and effective stress coping methods.

Supportive and Social Interventions:

Engaging in support groups, involving family members in therapy, and building a strong social support system can be vital for recovery.

Continuation and Maintenance Treatment:

Once remission is achieved, patients should continue treatment for several months to years to prevent relapse. This may include ongoing therapy and/or medication.

Regular Follow-up and Monitoring:

Individuals should schedule routine follow-up meetings with their mental healthcare professional to evaluate their advancement, modify their treatment when necessary, and manage any emerging concerns.

Alternative and Complementary Therapies:

Some individuals find benefit from complementary therapies like yoga, meditation, acupuncture, or herbal supplements. These should be used as adjuncts to, rather than substitutes for, evidence-based treatments.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Lifestyle modifications in treating Major depressive disorder

Creating a Supportive Home Environment:

Surround yourself with supportive and understanding family members or friends.

Ensure your living space is tidy and organized to reduce unnecessary stressors.

Consider decorating your home with soothing colors and comforting elements.

Minimize Stressors:

Identify and eliminate or reduce sources of stress in your daily life. This may include simplifying your schedule, delegating tasks, or setting boundaries with work and social commitments.

Create a quiet space where you can retreat to when you need solitude and relaxation.

Natural Light and Fresh Air:

Ensure your living space receives adequate natural light during the day, which can help regulate your circadian rhythm and improve mood.

Open windows regularly to let in fresh air, which can help combat feelings of stagnation.

Physical Exercise Environment:

Set up a home exercise area or join a nearby gym to encourage regular physical activity, which has been shown to have a positive impact on mood.

Decorate your exercise space with motivating and inspirational elements.

Healthy Eating Environment:

Organize your kitchen for healthy eating by stocking it with nutritious foods and removing tempting, unhealthy options.

Create a pleasant dining area where you can enjoy your meals mindfully.

Limit Digital Overload:

Reduce exposure to negative or distressing content on social media and news platforms.

Set boundaries for screen time and create tech-free zones in your home.

Mindfulness and Relaxation Zones:

Dedicate a space for mindfulness, meditation, or relaxation exercises.

Personalize this area with calming colors, comfortable seating, and soothing music or nature sounds.

Engage in Creative Activities:

Set up a creative workspace where you can explore artistic or hobby-related activities.

Engaging in creative outlets can help alleviate symptoms of depression.

Establish a Routine:

Develop a daily routine that includes regular sleep patterns and structured activities.

Having a predictable schedule can provide a sense of stability and control.

Social Interaction Space:

Create a space in your home for socializing with friends and loved ones.

Hosting gatherings in a comfortable environment can foster social connections.

Therapeutic Environment:

If you’re in therapy, consider setting up a designated area for virtual therapy sessions.

Ensure the space is private, comfortable, and free from distractions.

Nature and Greenery:

Incorporate indoor plants or a small garden if possible, as exposure to nature can have mood-lifting effects.

Top of Form

 

Effectiveness of Selective serotonin reuptake inhibitors in treating major depressive disorder

fluoxetine (Prozac):

This is one of the oldest SSRIs and has a long half-life, which means it stays in the body for a longer duration compared to some other SSRIs. Fluoxetine works to inhibits the reuptake of serotonin by neurons. It is prescribed for many conditions which include posttraumatic stress disorder and social anxiety disorder.

sertraline (Zoloft):

sertraline is often prescribed for MDD. It’s also approved for the treatment of various anxiety disorders. Sertraline is often used to treat MDD and various anxiety disorders. It is considered relatively well-tolerated.

paroxetine (Paxil):

paroxetine is another SSRI that is used in the treatment of MDD. It can also be prescribed for other conditions, such as panic disorder & generalized anxiety disorder. paroxetine impacts brain chemicals that might become imbalanced in individuals experiencing anxiety, depression, or related conditions. It exhibits minor anticholinergic effects and has the potential to induce greater weight gain compared to other selective serotonin reuptake inhibitors.

escitalopram (Lexapro):

escitalopram is the S-enantiomer of citalopram, which means it’s a more refined version of the medication. It is often considered well-tolerated and effective in the treatment of MDD.

citalopram (Celexa):

citalopram is an older SSRI that is still prescribed for MDD in some cases. Patients with a sustained corrected QT interval exceeding 500 ms should discontinue the use of Citalopram.

Role of Serotonin-norepinephrine reuptake inhibitors in treating Major depressive disorder

venlafaxine (Effexor):

venlafaxine is Primary treatment option, especially for individuals experiencing substantial fatigue or pain symptoms linked to their depressive episode. Venlafaxine is used to treat MDD, & various anxiety disorders. It comes in immediate-release and extended-release (XR) formulations.

duloxetine (Cymbalta):

duloxetine is approved for the treatment of MDD, GAD, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. It is also a primary treatment option for individuals who experience substantial fatigue or pain symptoms linked to their depressive episode.

desvenlafaxine (Pristiq):

desvenlafaxine is very closely related to venlafaxine, as it is the active metabolite of venlafaxine. It is primarily used to treat MDD and comes in an extended-release form.

levomilnacipran (Fetzima):

levomilnacipran is used to treat MDD. It may be an option for individuals who have not responded well to other antidepressants. It is also a primary treatment option for individuals who experience substantial fatigue or pain symptoms linked to their depressive episode.

Effectiveness of Tricyclic antidepressants in treating Major depressive disorder

amitriptyline:

amitriptyline is used not only for depression but also for conditions like chronic pain and migraine prevention. It elevates serotonin and norepinephrine concentrations within the brain.

imipramine:

imipramine is one of the first TCAs developed and has been used to treat depression and various anxiety disorders. Like other TCAs, it also affects serotonin and norepinephrine levels.

clomipramine:

clomipramine is primarily used to treat obsessive-compulsive disorder (OCD) but can also be used for depression. It has a more selective action on serotonin reuptake.

doxepin:

doxepin is sometimes used for depression and is also used at lower doses for sleep disorders due to its sedative effects. It affects both serotonin and norepinephrine levels.

nortriptyline:

nortriptyline is a metabolite of amitriptyline and is used for the treatment of depression. It is considered to have a somewhat milder side effect profile compared to some other TCAs.

Role of Serotonin modulators in treating Major depressive disorder

trazodone:

trazodone is an atypical antidepressant primarily used to treat depression but is also prescribed for insomnia due to its sedative properties.

It works by elevating serotonin levels in the brain through the inhibition of its reuptake, a mechanism shared with numerous other antidepressant medications.

Trazodone is often chosen when sleep problems are a significant component of the depressive disorder, as it can help with sleep initiation and maintenance.

vilazodone:

vilazodone is a newer antidepressant.

It is used to treat MDD and works by enhancing levels of serotonin in the brain and modulating serotonin receptor activity.

vortioxetine:

vortioxetine is another newer antidepressant that has a unique mechanism of action. It falls under the category of a serotonin modulator and stimulator.

It not only increases serotonin levels but also influences other neurotransmitters like norepinephrine and serotonin receptors.

vortioxetine is sometimes chosen when cognitive symptoms such as poor concentration and decision-making are prominent in MDD.

Effectiveness of Monoamine oxidase inhibitors (MAOIs) in treating major depressive disorder

tranylcypromine:

tranylcypromine is an MAOI that is sometimes prescribed for MDD.

It is typically used when other antidepressant treatments have not been effective or well-tolerated.

phenelzine:

phenelzine is another MAOI used in the treatment of major depressive disorder.

phenelzine has dietary restrictions, and individuals taking this medication need to avoid foods and drinks high in tyramine.

It is used to treat the atypical depression type in adults.

Intervention & Therapies for major depressive disorder

Psychotherapy:

Initiate individual therapy sessions, such as Cognitive-Behavioral Therapy (CBT), Interpersonal Therapy (IPT), or Mindfulness-Based Cognitive Therapy (MBCT), depending on the patient’s specific symptoms and needs.

Encourage regular attendance and participation in therapy sessions to address negative thought patterns, emotional regulation, and interpersonal difficulties.

Phases of Management

Assessment and Diagnosis:

Proper assessment by a healthcare provider is crucial to diagnose MDD accurately.

Evaluation of symptoms, medical history, and potential underlying causes.

Acute Phase:

Immediate treatment is initiated to alleviate severe depressive symptoms.

Medication: Antidepressant medications such as SSRI, serotonin-norepinephrine reuptake inhibitors, or other classes of antidepressants may be prescribed.

Psychotherapy: Cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), or other evidence-based therapies can be beneficial.

Hospitalization: In more extreme instances, hospitalization might become imperative, particularly when there is a potential for self-inflicted harm or suicidal tendencies.

Continuation Phase:

Once acute symptoms are under control, treatment continues to prevent relapse.

Medication is typically continued, and dosages may be adjusted as needed.

Psychotherapy continues to address underlying issues and develop coping strategies.

Monitoring for side effects and assessing treatment response.

Maintenance Phase:

This phase aims to prevent further episodes of depression.

Medication may be continued at a lower dose.

Psychotherapy can help individuals maintain their progress and resilience.

Modifying one’s way of life, encompassing activities like physical fitness, dietary choices, and stress handling, has a substantial impact on deterring relapse.

Adjunctive Therapies:

Electroconvulsive therapy (ECT): Considered in severe, treatment-resistant cases.

Transcranial Magnetic Stimulation (TMS): An alternative for treatment-resistant depression.

Ketamine infusion therapy: An emerging treatment for severe depression.

Support and Education:

Education about depression and its management is essential for individuals and their families.

Support groups or individual counseling can provide emotional support and coping strategies.

Regular Follow-up:

Regular follow-up appointments with healthcare providers to monitor progress, adjust treatment plans, and address any emerging issues.

Adjustments to medications and therapy may be necessary over time.

Crisis Management:

Have a crisis plan in place in case of severe relapse or suicidal thoughts.

Knowing when and how to seek immediate help is crucial.

Holistic Self-Care:

Encourage patients to engage in self-care practices, including exercise, a balanced diet, adequate sleep, and stress management techniques.

Relapse Prevention:

Recognize the initial indicators of relapse and formulate plans to effectively manage them.

Continued therapy and medication adherence are crucial in preventing relapse.

 

Medication

 

modafinil

Initial dose:

100

mg

Tablet

Oral

once a day

3 - 7

days

Increased to 200 mg/day oral tablet based on the response,
Further, increase to 400 mg/day if tolerated



vortioxetine

10

mg/day

Tablet

Oral

initially, increase/decrease the dose based on patient tolerance



paroxetine

20

mg

orally

every day

and increase up to 20-50 mg/day orally
The Maximum dose for a day is 50 mg



desvenlafaxine 

50 - 400

mg

Tablet

Orally 

every day



Dose Adjustments

Renal impairment:
Mild (CrCl≥50ml/min): No dosage adjustment is necessary
Moderate (CrCl 30-50ml/min): Do not exceed 50mg/day orally
Severe (CrCl<30ml/min): Do not exceed 25mg/day orally or 50 mg orally
every other day
Hepatic impairment:
Moderate-severe:50mg orally every day
Do not exceed more than 100mg/day

duloxetine 

Indicated for major depressive disorder (MDD) :


40-60 mg orally daily 1 week
Initially start with 30 mg daily 1 week for adjustment before going with 60 mg
There is no evidence that doses > 60 mg/day confer additional benefit



bupropion 

Immediate release tablet- 100 mg orally every 12 hours. Increase the dose to 100 mg every 8 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours.

Sustained release tablet- 150 mg orally each day. Increase the dose to 150 mg every 12 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours.

Extended-release tablet- 150 mg orally each day. Increase the dose to 450 mg each day. If no clinical improvement is seen, maximize the dose up to 300 mg each day.

Aplenzin- 174 mg orally each day. Increase the dose after 4 days, to 348 mg. Do not increase the dose to more than 522 mg each day.

Forfivo XL- 450 mg orally each day Can be utilized in patients who already are receiving 300 mg/day of bupropion



bupropion 

Immediate release tablet- 100 mg orally every 12 hours. Increase the dose to 100 mg every 8 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours.

Sustained release tablet- 150 mg orally each day. Increase the dose to 150 mg every 12 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours.

Extended-release tablet- 150 mg orally each day. Increase the dose to 450 mg each day. If no clinical improvement is seen, maximize the dose up to 300 mg each day.

Aplenzin- 174 mg orally each day. Increase the dose after 4 days, to 348 mg. Do not increase the dose to more than 522 mg each day.

Forfivo XL- 450 mg orally each day
Can be utilized in patients who already are receiving 300 mg/day of bupropion



brexanolone 

For a total of 60 hours (2.5 days), administer ZULRESSO as a continuous intravenous (IV) infusion as follows:


0-4 (hrs): Initiate with a dosage of 30 mcg/kg per hour continuous intravenous (IV) infusion

4-24 (hrs): the dose be increased to 60 mcg/kg per hour continuous intravenous (IV) infusion

24-52 (hrs): the dose be increased to 90 mcg/kg per hour (For individuals who cannot tolerate 90 mcg/kg per hour, decrease dose to 60 mcg/kg per hour) continuous intravenous (IV) infusion

52-56 (hrs): reduce to 60 mcg/kg per hour continuous intravenous (IV) infusion

56-60 (hrs): reduce to 30 mcg/kg per hour continuous intravenous (IV) infusion



quetiapine 

Antidepressant extended-release formulation
On days 1 & 2: 50 mg orally in the evening
Day 3: The dose can be increased to 150 mg orally in the evening.
Dosage range: 150-300 mg/day
Insomnia (Off-label)
Initially, 25 mg orally daily at bedtime.
Alcohol Dependence (Off-label)
25-50 mg orally at bedtime; can be titrated; should not exceed more than 300 mg



tranylcypromine 

Indicated in patients who are irresponsive to other antidepressants
15 mg orally every 12 hours; increase the dose by 5 mg/dose every 1-3 weeks to obtain a sufficient response
Do not exceed the dose of more than 60 mg/day
Once the response gets adequate, slowly decrease the dose



buprenorphine/samidorphan 

For the treatment of major depressive disorder in individuals who have not responded well to traditional medications, the FDA approval is pending



bupropion 

Immediate-release tablet-
100 mg orally every 12 hours
Increase the dose to 100 mg every 8 hours
If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours
Sustained release tablet-
150 mg orally each day
Increase the dose to 150 mg every 12 hours
If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours
Extended-release tablet-
150 mg orally each day
Increase the dose to 150 mg every 12 hours after 3 weeks If no clinical improvement is seen, maximize the dose by up to 300 mg each day
Aplenzin-
174 mg orally each day
Increase the dose after 4 days to 348 mg
Do not increase the dose to more than 522 mg each day
Forfivo XL-
450 mg orally each day
It can be utilized in patients who already are receiving 300 mg/day of bupropion



sertraline 

Tablets
Initially, 50 mg orally each day
Increase the dose by 25 mg at an interval of one week
Do not exceed 200 mg each day

Capsules
Do not utilize it to start over the treatment
It is only available in the form of 150 mg and 200 mg
For the initial dosage, utilize another sertraline HCl product
In patients who are taking 100 mg or 125 mg of different sertraline HCl products for a minimum of 1 week, start with capsules
150 mg or 200 mg orally each day is used as a recommended dose
Do not exceed more than 200 mg each day



fluoxetine 

20 mg orally each day
Increase the dose by 20 mg/day every week
Do not exceed the dose of more than 80 mg orally each day
90 mg of a delayed-release capsule can be taken each week orally



fluoxetine 

10 mg/day orally each day
Increase the dose by 10-20 mg/day after several weeks according to tolerance
Unless sedation occurs, do not take the medication at night



escitalopram 

Indicated for the treatment of acute and maintenance
10 mg orally each day
Increase the dose upto 20 mg/day after a week



escitalopram 

For more than 12 years- 10 mg orally each day
Increase the dose 3 weeks later
Do not exceed more than 20 mg/day



aripiprazole 

Initially, 2 to 5 mg/day orally; increased by 5 mg/day weekly whenever needed to a dosage range of 2 to 15 mg/day.



Dose Adjustments

Oral
Cytochrome-P 450 inhibitors and those with poor metabolism CYP2D6 poor metabolizers known: Administer half the usual dosage.

Poor metabolizers of CYP2D6 that utilize potent CYP3A4 inhibitors: Administer one-fourth of the prescribed dose (i.e., a 75% reduction).
Potent inhibitors of CYP2D6 or CYP3A4: Administer half the recommended dose Strong CYP3A4 inducers: twice the required dosage over 1-2 weeks.
Dosage Modifications (Abilify Maintena)
Poor metabolizers of CYP2D6: 300 mg Intramuscular
CYP2D6 poor metabolizers are taking a CYP3A4 inhibitor concurrently: 200 mg Intramuscular.
Patients taking 400 mg intramuscular
Strong CYP3A4 OR CYP2D6 inhibitors: 300 mg intramuscular
CYP3A4 And CYP2D6 inhibitors: 200 mg intramuscular
CYP3A4 inducers: Avoid usage

Patients taking 400 mg intramuscular
Strong CYP3A4 OR CYP2D6 inhibitors: 200 mg intramuscular
CYP3A4 And CYP2D6 inhibitors: 160 mg intramuscular
CYP3A4 inducers: Avoid usage

Dosage Modifications (Aristada)
There are no dose adjustments if CYP450 modulators are administered for less than two weeks.
Potent CYP3A4 inhibitor for more than two weeks
Lower the dosage to the next lowest strength. If 441 mg is tolerated, no dose change is required. Poor metabolizers of CYP2D6: Reduce the dose from 662 mg, 882 mg, or 1064 mg to 441 mg; if tolerated, there is no need to modify the dosage for individuals using 441 mg.
For more than two weeks, a potent CYP2D6 inhibitor was used:
Lower the dosage to the next lowest strength. If 441 mg is tolerated, no dose change is required.
Poor CYP2D6 metabolizers: There is no need to alter the dosage.

Both powerful CYP3A4 and CYP2D6 inhibitors were used for over two weeks:
Patients taking 662 mg, 882 mg, or 1064 mg should avoid using it. If 441 mg is tolerated, no dose change is required.

CYP3A4 inducers for more than two weeks:
There is no need to change the dosage to 662 mg, 882 mg, or 1064 mg. Increase the dosage from 441 mg to 662 mg.

Dosage Modifications (Aristada inito)
Poor CYP2D6 metabolizers, potent CYP3A4 inhibitors, and potent CYP3A4 inducers: Avoid using

Hepatic Impairment
Mild-to-severe (Child-Pugh score 5-15): There is no need for a dose change.

Renal Impairment
Mild-to-severe (GFR 15-90 mL/min): No dose changes are required.

Dosage Modifications (Abilify Asimtufii)
Poor CYP2D6 metabolizers
Poor CYP2D6 metabolizers: 720 mg every two months
Avoid usage if you are a known CYP2D6-poor metabolizer taking a CYP3A4 inhibitor.
Coadministration of CYP2D6 inhibitors-Patients on 960 mg should be reduced to 720 mg every two months.
Coadministration of CYP3A4 inhibitors-Patients on 960 mg should be reduced to 720 mg every two months.
Patients using 960 mg: Avoid coadministration with strong CYP2D6 and CY3A4 inhibitors.
Patients using 960 mg should avoid coadministration with potent CY3A4 inducers.

vilazodone 

10 mg orally once a day with food; following may increase to 20 mg every Day with food after seven days
the dosage may be increased further up to 40 mg/day, after a minimum of 7 days.
Optimal daily dosage for maintenance: 20–40 mg



Dose Adjustments

Dosing Considerations
Patients receiving 40 mg/day should decrease their dosage to 20 mg every Day for 4 days, then 10 mg every Day for 3 days. Patients taking 20 mg/day should taper their dosage to 10 mg every Day for 7 days.
Changing to or from MAO inhibitor therapy
For treating psychiatric disorders, vilazodone should not be given within 14 days of stopping an MAO inhibitor and starting vilazodone.
When treating psychiatric disorders, do not administer a MAO inhibitor within 14 days after stopping vilazodone and starting MAO medication.
Dosing Modifications
Renal impairment: dose adjustment is not recommended
Hepatic impairment: dose adjustment is not recommended
Coadministration with CYP3A4 inhibitors
strong CYP3A4 inhibitors (eg, ketoconazole): sholud not exceed more than 20 mg orally every Day
moderate CYP3A4 inhibitors (eg, erythromycin): decrease dose to 20 mg/day
Coadministration with CYP3A4 inducers
strong CYP3A4 inducers (eg, carbamazepine) for more than 14 days: should not exceed more than 80 mg/day
Dosing Considerations
Before starting treatment, check patients for a personal or family history of mania, hypomania, or bipolar illness.

levomilnacipran 

20 mg orally evey Day for 2 days; following
Increase to 40 mg orally every Day
Increase dosage in increments of 40 mg/day at intervals of two or more days based on effectiveness and tolerability; should not exceed more than 120 mg/day
range: 40-120 mg daily



Dose Adjustments

Dosage Modifications
Strong CYP3A4 inhibitors: should not exceed more than 80 mg/day levomilnacipran maintenance dose
Hepatic impairment: dosage adjustment is not required
Renal impairment
Mild (CrCl 60-89 mL/min): dosage adjustment is not required
Moderate (CrCl 30-59 mL/min): should not exceed more than 80 mg/day maintenance dose
Severe (CrCl 15-29 mL/min): should not exceed more than 40 mg/day maintenance dose
Not recommended to use in end-stage renal disease

psilocybin 

0.2 - 0.42

mg/kg

Pill

Orally 

Single dose



Note:
Certain individuals also experiment with microdosing psilocybin, yet there exists insufficient credible data to determine the suitable microdose quantity



 

duloxetine 


40-60 mg orally daily 1 week
Initially start with 30 mg daily 1 week for adjustment before going with 60 mg
There is no evidence that doses > 60 mg/day confer additional benefit



brexanolone 

For a total of 60 hours (2.5 days), administer ZULRESSO as a continuous intravenous (IV) infusion as follows:


Age: >15 years

0-4 (hrs): Initiate with a dosage of 30 mcg/kg per hour continuous intravenous (IV) infusion

4-24 (hrs): the dose be increased to 60 mcg/kg per hour continuous intravenous (IV) infusion

24-52 (hrs): the dose be increased to 90 mcg/kg per hour (For individuals who cannot tolerate 90 mcg/kg per hour, decrease dose to 60 mcg/kg per hour) continuous intravenous (IV) infusion

52-56 (hrs): reduce to 60 mcg/kg per hour continuous intravenous (IV) infusion

56-60 (hrs): reduce to 30 mcg/kg per hour continuous intravenous (IV) infusion



fluoxetine 

For more than eight years- Initially, 20 mg orally each day
Start the dose at 10 mg/day in children with less weight
Do not exceed the dose of more than 20 mg orally each day



 

vortioxetine

5

mg/day

Tablet

Oral

initially, increase up to 10 mg/day if tolerated



sertraline 

Initially, 25 mg/day orally each day
Increase the dose by 25 mg every 2-3 days
Do not exceed the dose of more than 200 mg orally each day
In depression due to Alzheimer’s and dementia, initially 12.5 mg/day and then titrate every 1-2 weeks
Do not exceed more than 150-200 mg



fluoxetine 

10 mg/day orally each day
Increase the dose by 10-20 mg/day after several weeks according to tolerance
Unless sedation occurs, do not take the medication at night



escitalopram 

Major Depressive Disorder
10 mg orally each day
No add-on benefits are seen with 20 mg/day



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Major Depressive disorder

Updated : September 12, 2023




Major Depressive Disorder is a widespread and incapacitating mental health disorder that impacts countless people around the globe. It transcends age, gender, and cultural boundaries, making it one of the most prevalent psychiatric disorders. Major Depressive Disorder often experience a range of symptoms, including changes in sleep patterns, appetite, energy levels, and concentration, which can interfere with their daily functioning.

This disorder casts a long and looming shadow over the lives of those who grapple with it, influencing their emotional well-being, physical health, relationships, and overall quality of life.

Prevalence:

The lifetime prevalence of MDD is 5-17%

Average prevalence rate is 12 %.

Age of Onset:

MDD can affect individuals of all ages, but the typical age of onset is in late adolescence to early adulthood.

Gender Differences:

Women are about twice as likely as men to be diagnosed with MDD.

Biological, hormonal, and sociocultural factors may influence gender differences in MDD.

Socioeconomic Factors:

Socioeconomic status can impact the risk of MDD.

People from lower socioeconomic backgrounds may have a higher risk due to factors like limited access to healthcare, stressors, and socioeconomic disparities.

Geographic Variations:

The prevalence and incidence of MDD can vary significantly between countries and regions.

Factors like cultural norms, healthcare access, and socioeconomic conditions contribute to these variations.

Risk Factors:

Risk factors including genetics, family history, traumatic life events, chronic stress, and personality traits.

Neurochemical Imbalances:

Dysregulation of neurotransmitters: One of the leading theories in depression’s pathophysiology is the dysregulation of neurotransmitters, particularly serotonin, norepinephrine, and dopamine. Reduced levels of these neurotransmitters in certain brain regions can lead to mood disturbances and depressive symptoms.

Neuroendocrine Dysregulation:

Hypothalamic-Pituitary-Adrenal (HPA) Axis: The dysregulation of the HPA axis can lead to an overproduction of stress hormones, including cortisol. Persistent exposure to heightened cortisol levels can bring about alterations in both mood and cognitive functioning, potentially playing a role in the onset of depression.

Inflammatory Processes:

There is growing evidence of a link between inflammation and depression. Chronic inflammation, often indicated by elevated levels of inflammatory markers like cytokines, may contribute to depressive symptoms. Inflammatory processes can affect neurotransmitter metabolism and neural plasticity.

Genetic Factors:

Family and twin research indicate an inherited inclination toward depression, with a genetic component playing a role. It is widely accepted that multiple genes contribute to an individual’s susceptibility to depression, and each gene is thought to exert a modest influence. However, the specific genes responsible for this predisposition are still the subject of ongoing research.

Environmental Factors:

Stressful life events: Traumatic or highly stressful life events, especially during childhood or early adulthood, can increase the risk of developing depression.

Biological Factors:

Neurotransmitter Imbalance: One of the most well-established biological factors is the imbalance of certain neurotransmitters in the brain, neurotransmitters like dopamine, serotonin and norepinephrine are pivotal in the regulation of mood. Imbalances in these neurotransmitter levels have been linked to the manifestation of depressive symptoms.

Genetic Factors:

Evidence suggests that a family history of depression can increase an individual’s risk of developing MDD. Genetic studies have identified specific gene variations that may predispose some to depression.

Psychological Factors:

Cognitive Factors: Negative thought patterns, cognitive biases, and distorted thinking can contribute to the onset and persistence of depressive symptoms. This is often a focus of cognitive-behavioral therapy (CBT), a common treatment for MDD.

Environmental Factors:

Stressful Life Events: Traumatic experiences, chronic stress, loss of a loved one, financial difficulties, or major life changes can trigger or exacerbate depressive episodes in susceptible individuals.

Childhood Adversity: Experiences of abuse, neglect, or other adverse childhood events can increase the risk of developing MDD later in life.

Psychosocial Factors: Social support, stressors, and life events can impact the prognosis of MDD. Positive social support can enhance recovery, while ongoing stressors can worsen symptoms.

Suicidal Ideation: The presence of suicidal thoughts or behaviors is a serious concern in MDD and can impact prognosis. Individuals with a history of suicide attempts or persistent suicidal ideation may have a higher risk of recurrent episodes and a more complex course.

Cognitive Functioning: Impairments in cognitive functioning, such as difficulties with concentration and memory, can affect prognosis and functional outcomes.

Substance Use: Substance abuse or dependence can complicate the course of MDD and is associated with a less favorable prognosis.

Age group:

Children and Adolescents: MDD can occur in children and teenagers. It’s often characterized by symptoms like irritability, social withdrawal, changes in appetite, and academic decline.

Adults: MDD is most diagnosed in adults. It can affect individuals throughout their adult life, from early adulthood to late adulthood.

Elderly: Depression can also affect older adults. In this age group, it might be associated with factors like chronic illness, loss of loved ones, and social isolation.

Across the Lifespan: MDD can affect people at any age, and its presentation may vary depending on the individual’s developmental stage and life circumstances.

Vital Signs:

Measure the patient’s blood pressure, pulse rate, respiratory rate, and body temperature.

Neurological Examination:

Evaluate coordination, reflexes, muscle strength, and sensation.

Assess for any neurological deficits that could indicate other medical conditions.

Gastrointestinal System:

Inquire about appetite and weight changes, as significant alterations may be indicative of an underlying medical condition.

Medication and Substance Use:

Ask about current medications, including over the counter and herbal supplements, as well as any substance use, including alcohol and illicit drugs, which can influence mood.

Sleep Patterns:

Discuss the patient’s sleep habits and any sleep disturbances, as sleep problems often co-occur with depression.

Anxiety Disorders: Major Depressive Disorder frequently occurs alongside various anxiety disorders. The shared symptoms of depression and anxiety can result in a more complex clinical manifestation.

Substance Abuse: People experiencing Major Depressive Disorder may resort to alcohol or drug usage as a means of dealing with the challenges posed by their depressive symptoms. This can lead to substance use disorders, making it essential to address both conditions simultaneously.

Suicidal Thoughts or Behaviors: Severe depression can increase the risk of suicidal ideation and self-harm. It’s crucial for individuals with MDD to seek help and support from mental health professionals if they experience these thoughts or behaviors.

Eating Disorders: Conditions like anorexia nervosa, bulimia nervosa, or binge-eating disorder may co-occur with MDD. These disorders often involve distorted body image and unhealthy relationships with food.

Chronic Pain: Depression and chronic pain frequently coexist. Chronic pain conditions like fibromyalgia or arthritis can contribute to the development or exacerbation of MDD, & Depression has the potential to amplify the experience of pain.

Sleep Disturbances: Many individuals with MDD experience disrupted sleep patterns, such as insomnia or hypersomnia (excessive sleep). These disturbances can worsen depressive symptoms and vice versa.

Social Isolation: Depression often leads to social withdrawal and isolation. Isolation and an absence of a strong social network can enhance the endurance of depressive manifestations and enhance sentiments of hopelessness.

Cognitive Impairment: Depression can affect cognitive functions such as memory, attention, and decision-making. This can impact a person’s ability to work or perform daily activities.

Reduced Physical Activity: People who have Major Depressive Disorder (MDD) may experience a decrease in their physical activity levels, potentially resulting in the adoption of a sedentary way of life. Lack of exercise can worsen both physical and mental health.

Negative Impact on Relationships: Depression can strain relationships with family and friends. The withdrawal, irritability, and sadness associated with depression can make it challenging to maintain healthy social connections.

Poor Academic or Occupational Performance: Depression can lead to decreased concentration and motivation, which can affect academic and occupational performance. This can result in decreased productivity and satisfaction in these areas.

Acute Onset: Some individuals may experience a sudden and acute onset of MDD symptoms. They might go from feeling relatively fine to severely depressed within a short period. A significant life event, trauma, or stressor can trigger this.

Chronic or Persistent: In other cases, the acuity may be less pronounced, and the symptoms may develop gradually over time. These individuals may have a long history of low-level depressive symptoms that have gradually worsened, leading to the diagnosis of MDD.

Severe Symptoms: Acuity can also be reflected in the severity of symptoms. Some individuals may experience very severe symptoms, including intense feelings of despair, suicidal thoughts, and physical symptoms like significant changes in weight or sleep patterns.

Moderate Symptoms: Others may have a more moderate presentation, with symptoms that interfere with daily life but are not as severe. They may still experience significant distress and impairment in functioning but not to the same extent as those with severe symptoms.

Atypical Features: Some individuals may present with atypical features of MDD, such as increased sleep, increased appetite, and leaden paralysis. These atypical symptoms can impact the acuity of the presentation and make it challenging to diagnose.

Recurrent Episodes: For some, MDD may be recurrent, with episodes of acute symptoms separated by periods of remission. The acuity can vary from episode to episode, with some being more severe than others.

Bipolar Disorder: Periods of sadness (like MDD) alternate with periods of mania or hypomania in bipolar disorder. Distinguishing between MDD and bipolar disorder can be challenging due to overlapping depressive symptoms.

Persistent Depressive Disorder (Dysthymia): Dysthymia is a chronic form of depression characterized by milder, but long-lasting depressive symptoms. It may be considered when symptoms persist for at least two years.

Adjustment Disorder with Depressed Mood: This condition occurs in response to a specific stressor or life event and leads to symptoms of depression. It is typically time-limited and resolves when the stressor is removed.

Post-Traumatic Stress Disorder (PTSD): PTSD can include symptoms such as persistent negative mood, emotional numbing, and loss of interest in activities, which may overlap with depressive symptoms.

Substance-Induced Mood Disorder: Substance abuse or withdrawal from certain substances (e.g., alcohol, drugs) can mimic the symptoms of depression. A thorough history of substance use is essential in the evaluation.

Initial Assessment and Diagnosis:

Comprehensive evaluation conducted by a certified mental health expert for the purpose of diagnosing Major Depressive Disorder (MDD) and eliminating the possibility of other concurrent medical or psychiatric disorders.

Psychoeducation:

Educating the patient and their family about depression, its symptoms, and the treatment options available.

Psychotherapy:

Cognitive-Behavioral Therapy (CBT): A systematic and purpose-driven strategy designed to assist individuals in recognizing and modifying detrimental thought patterns and behaviors that are exacerbating their depression.

Psychodynamic Therapy: Exploring unconscious conflicts and past experiences that may be contributing to depression.

Behavioral Activation: Encouraging engagement in rewarding activities to counteract the withdrawal and isolation often associated with depression.

Mindfulness-Based Cognitive Therapy (MBCT): Combining mindfulness techniques with CBT to prevent depressive relapse.

Pharmacotherapy:

Antidepressant Medications: Depending on the severity and type of depression, antidepressant medications such as SSRIs, SNRIs and Norepinephrine Reuptake Inhibitors, or other classes of drugs may be prescribed. It’s crucial to monitor for side effects and therapeutic response.

Adjunctive Medications: In some cases, other medications like mood stabilizers or atypical antipsychotics may be added to the treatment regimen, especially when there are symptoms of anxiety or mood instability.

Medication management should involve close monitoring by a psychiatrist, including regular assessments of medication effectiveness and potential side effects.

Electroconvulsive Therapy (ECT):

ECT may be considered when depression is severe, treatment-resistant, or when rapid symptom relief is essential. It’s typically administered under general anesthesia by a specialized team.

Lifestyle Modifications:

Promoting patients to embrace a wholesome way of life, encompassing routine physical activity, a well-rounded nutritional regimen, sufficient rest, and effective stress coping methods.

Supportive and Social Interventions:

Engaging in support groups, involving family members in therapy, and building a strong social support system can be vital for recovery.

Continuation and Maintenance Treatment:

Once remission is achieved, patients should continue treatment for several months to years to prevent relapse. This may include ongoing therapy and/or medication.

Regular Follow-up and Monitoring:

Individuals should schedule routine follow-up meetings with their mental healthcare professional to evaluate their advancement, modify their treatment when necessary, and manage any emerging concerns.

Alternative and Complementary Therapies:

Some individuals find benefit from complementary therapies like yoga, meditation, acupuncture, or herbal supplements. These should be used as adjuncts to, rather than substitutes for, evidence-based treatments.

Creating a Supportive Home Environment:

Surround yourself with supportive and understanding family members or friends.

Ensure your living space is tidy and organized to reduce unnecessary stressors.

Consider decorating your home with soothing colors and comforting elements.

Minimize Stressors:

Identify and eliminate or reduce sources of stress in your daily life. This may include simplifying your schedule, delegating tasks, or setting boundaries with work and social commitments.

Create a quiet space where you can retreat to when you need solitude and relaxation.

Natural Light and Fresh Air:

Ensure your living space receives adequate natural light during the day, which can help regulate your circadian rhythm and improve mood.

Open windows regularly to let in fresh air, which can help combat feelings of stagnation.

Physical Exercise Environment:

Set up a home exercise area or join a nearby gym to encourage regular physical activity, which has been shown to have a positive impact on mood.

Decorate your exercise space with motivating and inspirational elements.

Healthy Eating Environment:

Organize your kitchen for healthy eating by stocking it with nutritious foods and removing tempting, unhealthy options.

Create a pleasant dining area where you can enjoy your meals mindfully.

Limit Digital Overload:

Reduce exposure to negative or distressing content on social media and news platforms.

Set boundaries for screen time and create tech-free zones in your home.

Mindfulness and Relaxation Zones:

Dedicate a space for mindfulness, meditation, or relaxation exercises.

Personalize this area with calming colors, comfortable seating, and soothing music or nature sounds.

Engage in Creative Activities:

Set up a creative workspace where you can explore artistic or hobby-related activities.

Engaging in creative outlets can help alleviate symptoms of depression.

Establish a Routine:

Develop a daily routine that includes regular sleep patterns and structured activities.

Having a predictable schedule can provide a sense of stability and control.

Social Interaction Space:

Create a space in your home for socializing with friends and loved ones.

Hosting gatherings in a comfortable environment can foster social connections.

Therapeutic Environment:

If you’re in therapy, consider setting up a designated area for virtual therapy sessions.

Ensure the space is private, comfortable, and free from distractions.

Nature and Greenery:

Incorporate indoor plants or a small garden if possible, as exposure to nature can have mood-lifting effects.

Top of Form

 

fluoxetine (Prozac):

This is one of the oldest SSRIs and has a long half-life, which means it stays in the body for a longer duration compared to some other SSRIs. Fluoxetine works to inhibits the reuptake of serotonin by neurons. It is prescribed for many conditions which include posttraumatic stress disorder and social anxiety disorder.

sertraline (Zoloft):

sertraline is often prescribed for MDD. It’s also approved for the treatment of various anxiety disorders. Sertraline is often used to treat MDD and various anxiety disorders. It is considered relatively well-tolerated.

paroxetine (Paxil):

paroxetine is another SSRI that is used in the treatment of MDD. It can also be prescribed for other conditions, such as panic disorder & generalized anxiety disorder. paroxetine impacts brain chemicals that might become imbalanced in individuals experiencing anxiety, depression, or related conditions. It exhibits minor anticholinergic effects and has the potential to induce greater weight gain compared to other selective serotonin reuptake inhibitors.

escitalopram (Lexapro):

escitalopram is the S-enantiomer of citalopram, which means it’s a more refined version of the medication. It is often considered well-tolerated and effective in the treatment of MDD.

citalopram (Celexa):

citalopram is an older SSRI that is still prescribed for MDD in some cases. Patients with a sustained corrected QT interval exceeding 500 ms should discontinue the use of Citalopram.

venlafaxine (Effexor):

venlafaxine is Primary treatment option, especially for individuals experiencing substantial fatigue or pain symptoms linked to their depressive episode. Venlafaxine is used to treat MDD, & various anxiety disorders. It comes in immediate-release and extended-release (XR) formulations.

duloxetine (Cymbalta):

duloxetine is approved for the treatment of MDD, GAD, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. It is also a primary treatment option for individuals who experience substantial fatigue or pain symptoms linked to their depressive episode.

desvenlafaxine (Pristiq):

desvenlafaxine is very closely related to venlafaxine, as it is the active metabolite of venlafaxine. It is primarily used to treat MDD and comes in an extended-release form.

levomilnacipran (Fetzima):

levomilnacipran is used to treat MDD. It may be an option for individuals who have not responded well to other antidepressants. It is also a primary treatment option for individuals who experience substantial fatigue or pain symptoms linked to their depressive episode.

amitriptyline:

amitriptyline is used not only for depression but also for conditions like chronic pain and migraine prevention. It elevates serotonin and norepinephrine concentrations within the brain.

imipramine:

imipramine is one of the first TCAs developed and has been used to treat depression and various anxiety disorders. Like other TCAs, it also affects serotonin and norepinephrine levels.

clomipramine:

clomipramine is primarily used to treat obsessive-compulsive disorder (OCD) but can also be used for depression. It has a more selective action on serotonin reuptake.

doxepin:

doxepin is sometimes used for depression and is also used at lower doses for sleep disorders due to its sedative effects. It affects both serotonin and norepinephrine levels.

nortriptyline:

nortriptyline is a metabolite of amitriptyline and is used for the treatment of depression. It is considered to have a somewhat milder side effect profile compared to some other TCAs.

trazodone:

trazodone is an atypical antidepressant primarily used to treat depression but is also prescribed for insomnia due to its sedative properties.

It works by elevating serotonin levels in the brain through the inhibition of its reuptake, a mechanism shared with numerous other antidepressant medications.

Trazodone is often chosen when sleep problems are a significant component of the depressive disorder, as it can help with sleep initiation and maintenance.

vilazodone:

vilazodone is a newer antidepressant.

It is used to treat MDD and works by enhancing levels of serotonin in the brain and modulating serotonin receptor activity.

vortioxetine:

vortioxetine is another newer antidepressant that has a unique mechanism of action. It falls under the category of a serotonin modulator and stimulator.

It not only increases serotonin levels but also influences other neurotransmitters like norepinephrine and serotonin receptors.

vortioxetine is sometimes chosen when cognitive symptoms such as poor concentration and decision-making are prominent in MDD.

tranylcypromine:

tranylcypromine is an MAOI that is sometimes prescribed for MDD.

It is typically used when other antidepressant treatments have not been effective or well-tolerated.

phenelzine:

phenelzine is another MAOI used in the treatment of major depressive disorder.

phenelzine has dietary restrictions, and individuals taking this medication need to avoid foods and drinks high in tyramine.

It is used to treat the atypical depression type in adults.

Psychotherapy:

Initiate individual therapy sessions, such as Cognitive-Behavioral Therapy (CBT), Interpersonal Therapy (IPT), or Mindfulness-Based Cognitive Therapy (MBCT), depending on the patient’s specific symptoms and needs.

Encourage regular attendance and participation in therapy sessions to address negative thought patterns, emotional regulation, and interpersonal difficulties.

Assessment and Diagnosis:

Proper assessment by a healthcare provider is crucial to diagnose MDD accurately.

Evaluation of symptoms, medical history, and potential underlying causes.

Acute Phase:

Immediate treatment is initiated to alleviate severe depressive symptoms.

Medication: Antidepressant medications such as SSRI, serotonin-norepinephrine reuptake inhibitors, or other classes of antidepressants may be prescribed.

Psychotherapy: Cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), or other evidence-based therapies can be beneficial.

Hospitalization: In more extreme instances, hospitalization might become imperative, particularly when there is a potential for self-inflicted harm or suicidal tendencies.

Continuation Phase:

Once acute symptoms are under control, treatment continues to prevent relapse.

Medication is typically continued, and dosages may be adjusted as needed.

Psychotherapy continues to address underlying issues and develop coping strategies.

Monitoring for side effects and assessing treatment response.

Maintenance Phase:

This phase aims to prevent further episodes of depression.

Medication may be continued at a lower dose.

Psychotherapy can help individuals maintain their progress and resilience.

Modifying one’s way of life, encompassing activities like physical fitness, dietary choices, and stress handling, has a substantial impact on deterring relapse.

Adjunctive Therapies:

Electroconvulsive therapy (ECT): Considered in severe, treatment-resistant cases.

Transcranial Magnetic Stimulation (TMS): An alternative for treatment-resistant depression.

Ketamine infusion therapy: An emerging treatment for severe depression.

Support and Education:

Education about depression and its management is essential for individuals and their families.

Support groups or individual counseling can provide emotional support and coping strategies.

Regular Follow-up:

Regular follow-up appointments with healthcare providers to monitor progress, adjust treatment plans, and address any emerging issues.

Adjustments to medications and therapy may be necessary over time.

Crisis Management:

Have a crisis plan in place in case of severe relapse or suicidal thoughts.

Knowing when and how to seek immediate help is crucial.

Holistic Self-Care:

Encourage patients to engage in self-care practices, including exercise, a balanced diet, adequate sleep, and stress management techniques.

Relapse Prevention:

Recognize the initial indicators of relapse and formulate plans to effectively manage them.

Continued therapy and medication adherence are crucial in preventing relapse.

 

modafinil

Initial dose:

100

mg

Tablet

Oral

once a day

3 - 7

days

Increased to 200 mg/day oral tablet based on the response,
Further, increase to 400 mg/day if tolerated



vortioxetine

10

mg/day

Tablet

Oral

initially, increase/decrease the dose based on patient tolerance



paroxetine

20

mg

orally

every day

and increase up to 20-50 mg/day orally
The Maximum dose for a day is 50 mg



desvenlafaxine 

50 - 400

mg

Tablet

Orally 

every day



Dose Adjustments

Renal impairment:
Mild (CrCl≥50ml/min): No dosage adjustment is necessary
Moderate (CrCl 30-50ml/min): Do not exceed 50mg/day orally
Severe (CrCl<30ml/min): Do not exceed 25mg/day orally or 50 mg orally
every other day
Hepatic impairment:
Moderate-severe:50mg orally every day
Do not exceed more than 100mg/day

duloxetine 

Indicated for major depressive disorder (MDD) :


40-60 mg orally daily 1 week
Initially start with 30 mg daily 1 week for adjustment before going with 60 mg
There is no evidence that doses > 60 mg/day confer additional benefit



bupropion 

Immediate release tablet- 100 mg orally every 12 hours. Increase the dose to 100 mg every 8 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours.

Sustained release tablet- 150 mg orally each day. Increase the dose to 150 mg every 12 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours.

Extended-release tablet- 150 mg orally each day. Increase the dose to 450 mg each day. If no clinical improvement is seen, maximize the dose up to 300 mg each day.

Aplenzin- 174 mg orally each day. Increase the dose after 4 days, to 348 mg. Do not increase the dose to more than 522 mg each day.

Forfivo XL- 450 mg orally each day Can be utilized in patients who already are receiving 300 mg/day of bupropion



bupropion 

Immediate release tablet- 100 mg orally every 12 hours. Increase the dose to 100 mg every 8 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours.

Sustained release tablet- 150 mg orally each day. Increase the dose to 150 mg every 12 hours. If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours.

Extended-release tablet- 150 mg orally each day. Increase the dose to 450 mg each day. If no clinical improvement is seen, maximize the dose up to 300 mg each day.

Aplenzin- 174 mg orally each day. Increase the dose after 4 days, to 348 mg. Do not increase the dose to more than 522 mg each day.

Forfivo XL- 450 mg orally each day
Can be utilized in patients who already are receiving 300 mg/day of bupropion



brexanolone 

For a total of 60 hours (2.5 days), administer ZULRESSO as a continuous intravenous (IV) infusion as follows:


0-4 (hrs): Initiate with a dosage of 30 mcg/kg per hour continuous intravenous (IV) infusion

4-24 (hrs): the dose be increased to 60 mcg/kg per hour continuous intravenous (IV) infusion

24-52 (hrs): the dose be increased to 90 mcg/kg per hour (For individuals who cannot tolerate 90 mcg/kg per hour, decrease dose to 60 mcg/kg per hour) continuous intravenous (IV) infusion

52-56 (hrs): reduce to 60 mcg/kg per hour continuous intravenous (IV) infusion

56-60 (hrs): reduce to 30 mcg/kg per hour continuous intravenous (IV) infusion



quetiapine 

Antidepressant extended-release formulation
On days 1 & 2: 50 mg orally in the evening
Day 3: The dose can be increased to 150 mg orally in the evening.
Dosage range: 150-300 mg/day
Insomnia (Off-label)
Initially, 25 mg orally daily at bedtime.
Alcohol Dependence (Off-label)
25-50 mg orally at bedtime; can be titrated; should not exceed more than 300 mg



tranylcypromine 

Indicated in patients who are irresponsive to other antidepressants
15 mg orally every 12 hours; increase the dose by 5 mg/dose every 1-3 weeks to obtain a sufficient response
Do not exceed the dose of more than 60 mg/day
Once the response gets adequate, slowly decrease the dose



buprenorphine/samidorphan 

For the treatment of major depressive disorder in individuals who have not responded well to traditional medications, the FDA approval is pending



bupropion 

Immediate-release tablet-
100 mg orally every 12 hours
Increase the dose to 100 mg every 8 hours
If no clinical improvement is seen, maximize the dose up to 150 mg every 8 hours
Sustained release tablet-
150 mg orally each day
Increase the dose to 150 mg every 12 hours
If no clinical improvement is seen, maximize the dose up to 150 mg every 12 hours
Extended-release tablet-
150 mg orally each day
Increase the dose to 150 mg every 12 hours after 3 weeks If no clinical improvement is seen, maximize the dose by up to 300 mg each day
Aplenzin-
174 mg orally each day
Increase the dose after 4 days to 348 mg
Do not increase the dose to more than 522 mg each day
Forfivo XL-
450 mg orally each day
It can be utilized in patients who already are receiving 300 mg/day of bupropion



sertraline 

Tablets
Initially, 50 mg orally each day
Increase the dose by 25 mg at an interval of one week
Do not exceed 200 mg each day

Capsules
Do not utilize it to start over the treatment
It is only available in the form of 150 mg and 200 mg
For the initial dosage, utilize another sertraline HCl product
In patients who are taking 100 mg or 125 mg of different sertraline HCl products for a minimum of 1 week, start with capsules
150 mg or 200 mg orally each day is used as a recommended dose
Do not exceed more than 200 mg each day



fluoxetine 

20 mg orally each day
Increase the dose by 20 mg/day every week
Do not exceed the dose of more than 80 mg orally each day
90 mg of a delayed-release capsule can be taken each week orally



fluoxetine 

10 mg/day orally each day
Increase the dose by 10-20 mg/day after several weeks according to tolerance
Unless sedation occurs, do not take the medication at night



escitalopram 

Indicated for the treatment of acute and maintenance
10 mg orally each day
Increase the dose upto 20 mg/day after a week



escitalopram 

For more than 12 years- 10 mg orally each day
Increase the dose 3 weeks later
Do not exceed more than 20 mg/day



aripiprazole 

Initially, 2 to 5 mg/day orally; increased by 5 mg/day weekly whenever needed to a dosage range of 2 to 15 mg/day.



Dose Adjustments

Oral
Cytochrome-P 450 inhibitors and those with poor metabolism CYP2D6 poor metabolizers known: Administer half the usual dosage.

Poor metabolizers of CYP2D6 that utilize potent CYP3A4 inhibitors: Administer one-fourth of the prescribed dose (i.e., a 75% reduction).
Potent inhibitors of CYP2D6 or CYP3A4: Administer half the recommended dose Strong CYP3A4 inducers: twice the required dosage over 1-2 weeks.
Dosage Modifications (Abilify Maintena)
Poor metabolizers of CYP2D6: 300 mg Intramuscular
CYP2D6 poor metabolizers are taking a CYP3A4 inhibitor concurrently: 200 mg Intramuscular.
Patients taking 400 mg intramuscular
Strong CYP3A4 OR CYP2D6 inhibitors: 300 mg intramuscular
CYP3A4 And CYP2D6 inhibitors: 200 mg intramuscular
CYP3A4 inducers: Avoid usage

Patients taking 400 mg intramuscular
Strong CYP3A4 OR CYP2D6 inhibitors: 200 mg intramuscular
CYP3A4 And CYP2D6 inhibitors: 160 mg intramuscular
CYP3A4 inducers: Avoid usage

Dosage Modifications (Aristada)
There are no dose adjustments if CYP450 modulators are administered for less than two weeks.
Potent CYP3A4 inhibitor for more than two weeks
Lower the dosage to the next lowest strength. If 441 mg is tolerated, no dose change is required. Poor metabolizers of CYP2D6: Reduce the dose from 662 mg, 882 mg, or 1064 mg to 441 mg; if tolerated, there is no need to modify the dosage for individuals using 441 mg.
For more than two weeks, a potent CYP2D6 inhibitor was used:
Lower the dosage to the next lowest strength. If 441 mg is tolerated, no dose change is required.
Poor CYP2D6 metabolizers: There is no need to alter the dosage.

Both powerful CYP3A4 and CYP2D6 inhibitors were used for over two weeks:
Patients taking 662 mg, 882 mg, or 1064 mg should avoid using it. If 441 mg is tolerated, no dose change is required.

CYP3A4 inducers for more than two weeks:
There is no need to change the dosage to 662 mg, 882 mg, or 1064 mg. Increase the dosage from 441 mg to 662 mg.

Dosage Modifications (Aristada inito)
Poor CYP2D6 metabolizers, potent CYP3A4 inhibitors, and potent CYP3A4 inducers: Avoid using

Hepatic Impairment
Mild-to-severe (Child-Pugh score 5-15): There is no need for a dose change.

Renal Impairment
Mild-to-severe (GFR 15-90 mL/min): No dose changes are required.

Dosage Modifications (Abilify Asimtufii)
Poor CYP2D6 metabolizers
Poor CYP2D6 metabolizers: 720 mg every two months
Avoid usage if you are a known CYP2D6-poor metabolizer taking a CYP3A4 inhibitor.
Coadministration of CYP2D6 inhibitors-Patients on 960 mg should be reduced to 720 mg every two months.
Coadministration of CYP3A4 inhibitors-Patients on 960 mg should be reduced to 720 mg every two months.
Patients using 960 mg: Avoid coadministration with strong CYP2D6 and CY3A4 inhibitors.
Patients using 960 mg should avoid coadministration with potent CY3A4 inducers.

vilazodone 

10 mg orally once a day with food; following may increase to 20 mg every Day with food after seven days
the dosage may be increased further up to 40 mg/day, after a minimum of 7 days.
Optimal daily dosage for maintenance: 20–40 mg



Dose Adjustments

Dosing Considerations
Patients receiving 40 mg/day should decrease their dosage to 20 mg every Day for 4 days, then 10 mg every Day for 3 days. Patients taking 20 mg/day should taper their dosage to 10 mg every Day for 7 days.
Changing to or from MAO inhibitor therapy
For treating psychiatric disorders, vilazodone should not be given within 14 days of stopping an MAO inhibitor and starting vilazodone.
When treating psychiatric disorders, do not administer a MAO inhibitor within 14 days after stopping vilazodone and starting MAO medication.
Dosing Modifications
Renal impairment: dose adjustment is not recommended
Hepatic impairment: dose adjustment is not recommended
Coadministration with CYP3A4 inhibitors
strong CYP3A4 inhibitors (eg, ketoconazole): sholud not exceed more than 20 mg orally every Day
moderate CYP3A4 inhibitors (eg, erythromycin): decrease dose to 20 mg/day
Coadministration with CYP3A4 inducers
strong CYP3A4 inducers (eg, carbamazepine) for more than 14 days: should not exceed more than 80 mg/day
Dosing Considerations
Before starting treatment, check patients for a personal or family history of mania, hypomania, or bipolar illness.

levomilnacipran 

20 mg orally evey Day for 2 days; following
Increase to 40 mg orally every Day
Increase dosage in increments of 40 mg/day at intervals of two or more days based on effectiveness and tolerability; should not exceed more than 120 mg/day
range: 40-120 mg daily



Dose Adjustments

Dosage Modifications
Strong CYP3A4 inhibitors: should not exceed more than 80 mg/day levomilnacipran maintenance dose
Hepatic impairment: dosage adjustment is not required
Renal impairment
Mild (CrCl 60-89 mL/min): dosage adjustment is not required
Moderate (CrCl 30-59 mL/min): should not exceed more than 80 mg/day maintenance dose
Severe (CrCl 15-29 mL/min): should not exceed more than 40 mg/day maintenance dose
Not recommended to use in end-stage renal disease

psilocybin 

0.2 - 0.42

mg/kg

Pill

Orally 

Single dose



Note:
Certain individuals also experiment with microdosing psilocybin, yet there exists insufficient credible data to determine the suitable microdose quantity



duloxetine 


40-60 mg orally daily 1 week
Initially start with 30 mg daily 1 week for adjustment before going with 60 mg
There is no evidence that doses > 60 mg/day confer additional benefit



brexanolone 

For a total of 60 hours (2.5 days), administer ZULRESSO as a continuous intravenous (IV) infusion as follows:


Age: >15 years

0-4 (hrs): Initiate with a dosage of 30 mcg/kg per hour continuous intravenous (IV) infusion

4-24 (hrs): the dose be increased to 60 mcg/kg per hour continuous intravenous (IV) infusion

24-52 (hrs): the dose be increased to 90 mcg/kg per hour (For individuals who cannot tolerate 90 mcg/kg per hour, decrease dose to 60 mcg/kg per hour) continuous intravenous (IV) infusion

52-56 (hrs): reduce to 60 mcg/kg per hour continuous intravenous (IV) infusion

56-60 (hrs): reduce to 30 mcg/kg per hour continuous intravenous (IV) infusion



fluoxetine 

For more than eight years- Initially, 20 mg orally each day
Start the dose at 10 mg/day in children with less weight
Do not exceed the dose of more than 20 mg orally each day



vortioxetine

5

mg/day

Tablet

Oral

initially, increase up to 10 mg/day if tolerated



sertraline 

Initially, 25 mg/day orally each day
Increase the dose by 25 mg every 2-3 days
Do not exceed the dose of more than 200 mg orally each day
In depression due to Alzheimer’s and dementia, initially 12.5 mg/day and then titrate every 1-2 weeks
Do not exceed more than 150-200 mg



fluoxetine 

10 mg/day orally each day
Increase the dose by 10-20 mg/day after several weeks according to tolerance
Unless sedation occurs, do not take the medication at night



escitalopram 

Major Depressive Disorder
10 mg orally each day
No add-on benefits are seen with 20 mg/day



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