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Background
Schizophrenia is a mental disorder characterized by delusions, hallucinations (auditory or visual), and disturbances in thought, perception, behavior, and emotional responses.
Although the course of the disease varies from individual to individual, it is usually persistent and disabling.
It is detected in the late teen years to early thirties. The disease’s negative symptoms (Classic 5 A’s) are Affect (blunted), Alogia, Asociality, Avolition, and Anhedonia.
Epidemiology
The prevalence of schizophrenia is relatively high with early onset in adulthood and develops into a chronic condition. The prevalence varies globally, from 0.6 to 1.9% in the United States, affecting about 1% of the adult population.
Males are slightly affected more and have an early onset of the disease than females with a ratio of 4: 1. A 40% risk is estimated between the use of cannabis, cocaine, and schizophrenia.
Anatomy
Pathophysiology
Schizophrenia is mainly attributed to increased dopamine transmission in the brain’s mesolimbic pathway. In contrast, low dopamine levels in the nigrostriatal pathway are hypothesized to generate motor symptoms via an effect on the extrapyramidal system. Low levels of mesocortical dopamine are believed to induce the disease’s negative symptoms.
High prolactin levels cause other symptoms like decreased libido and amenorrhea due to the declined availability of tuberoinfundibular dopamine. Though serotonergic hyperactivity has been demonstrated to have a role in the development of schizophrenia, evidence suggests that glutaminergic hypoactivity is also involved.
NMDA receptor antagonists have been proven to exacerbate both positive and negative symptoms in schizophrenia. Schizophrenia results in a decrease in grey matter volume that affects both the parietal and temporal lobes. There are also alterations in the hippocampus and frontal lobes, which may be a factor in memory and cognitive impairments.
Etiology
Several theories postulate that abnormalities in neurotransmitters, such as glutaminergic and GABA hypoactivity or dopaminergic, serotonergic, and alpha-adrenergic hyperactivity, contribute to the development of schizophrenia. The gene neuregulin (NGR1) is involved in glutamate signaling and brain development.
Dysbindin (DTNBP1) promotes glutamate release, and catecholamine O-methyl transferase (COMT) polymorphism modulates dopamine function. Maternal malnutrition and vitamin D deficiency, pre-eclampsia, perinatal hypoxia, gestational diabetes, complications during birth, abnormal fetal development, and low birth weight increase the risk of developing this disease.
Genetics
A positive family history of schizophrenia in a first-degree relative has a 6.5% risk of transmission and the risk is increased in twins to more than 40%. Both parents with schizophrenia have a 60% risk of offspring being affected.
Prognostic Factors
The prognosis of the condition depends on several factors like age of onset, cognitive impairment, and co-morbid conditions. Suicide is the prime reason for premature mortality, and most patients report suicidal ideation. The estimated suicide rate is 4.9% in patients who lose their life from schizophrenia; it is observed in the early stage of the disease.
Clinical History
Clinical History
Schizophrenia typically begins to manifest in late adolescence or early adulthood. The patient may experience a gradual onset of symptoms or a sudden behavior change. Common initial symptoms include social withdrawal, decline in academic or occupational performance, increased irritability or agitation, and changes in sleep patterns.
Positive symptoms refer to the presence of abnormal experiences or behaviors that are not typically seen in healthy individuals. These symptoms may include:
Negative symptoms involve a loss or decrease in normal functioning or experiences. These symptoms may include:
Schizophrenia can also affect cognitive functioning, leading to problems with attention, memory, and executive functions (such as planning and decision-making). These cognitive impairments can significantly impact daily functioning and overall quality of life.
The symptoms of schizophrenia are chronic and can last for at least six months. The severity and duration of symptoms may vary over time, with periods of exacerbation and remission. The condition can significantly impact the patient’s relationships, education, employment, and overall functioning.
Physical Examination
Physical Examination
Schizophrenia is primarily a mental disorder, and its diagnosis is based on the presence of characteristic symptoms rather than physical findings. However, certain physical findings may be observed in individuals with schizophrenia, either as direct consequences of the illness or due to associated factors.
Motor Abnormalities:
Some individuals with schizophrenia may exhibit motor abnormalities, such as:
Motoric immobility: A decrease in spontaneous movement or voluntary actions.
Weight Changes: Schizophrenia can be associated with weight changes due to various factors, including side effects of antipsychotic medications or alterations in appetite and metabolism.
Movement Disorders: In some cases, individuals with schizophrenia may develop movement disorders, such as:
Self-neglect: In severe cases or during periods of active symptoms, individuals with schizophrenia may neglect their personal hygiene, appearance, and self-care, which can lead to physical signs like poor grooming, unkempt hair, and dirty clothing.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnoses
Delusional Disorder
Pervasive developmental disorder
Substance-induced psychotic disorder
Paranoid personality disorder
Schizotypal personality disorder
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
In the initial treatment of acute psychosis, it is recommended to begin with an oral second-generation antipsychotic medication. Examples of these medications include olanzapine, aripiprazole, risperidone, asenapine, quetiapine, lurasidone, sertindole, brexpiprazole, ziprasidone, molindone, iloperidone, and others.
In some instances, if clinically necessary, a benzodiazepine such as clonazepam, diazepam, or lorazepam may be prescribed alongside the antipsychotic to manage behavioral disturbances and non-acute anxiety.
While first-generation antipsychotics (FGA) like flupentixol, trifluoperazine, fluphenazine, pimozide, haloperidol, sulpiride, chlorpromazine, and others are not commonly used as first-line treatment, they can still be utilized if needed.
Cognitive behavioral therapy (CBT) and art and drama therapies can be beneficial in addressing the disease’s negative symptoms, improving insight, and preventing relapse. These approaches aim to counteract the negative impact of the disease and assist in the patient’s rehabilitation process.
Clozapine is reserved for cases of treatment resistance, with a poor response to at least two different antipsychotic medications. It requires close monitoring, including weekly blood tests for the first six months, biweekly tests for the following six months, and monthly tests to monitor the white blood cell count due to the risk of agranulocytosis.
During the maintenance phase of treatment, prophylaxis and rehabilitation efforts play a vital role in reintegrating patients into the community. It is important to establish the minimum effective dose of antipsychotics during this period.
Substance abuse is common among patients with schizophrenia and can worsen both positive and negative symptoms. Therefore, psychosocial and pharmacotherapeutic approaches should be employed to address substance misuse. In cases of extensive and persistent substance misuse, clozapine may be considered.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
0.5 - 5
mg
every 8 hrs
do not exceed the dose of more than 30 mg/day
5
mg
sublingually
every 12 hrs
a day; maybe increase to 10 mg sublingually 2 times a day
Do not exceed 20 mg per day
Day 1-4: 1mg orally every day
Day 5-7: Adjust dosage to 2 mg every day
Day 8: Adjust to 4mg/day
Do not exceed 4mg/day
Orally
Initially:2mg/day
At an interval of 24 hours, may increase the dose from 1-2mg/day
Maintenance dose:2 to 8mg orally/day
Maximum dose:16mg orally/day
Intramuscular
Initial dose:25mg intramuscular every two weeks
Titration dose: may increase up to 37.5mg or 50mg
Maximum dose: 50mg intramuscular every two weeks
Subcutaneous
90mg or 120mg subcutaneously monthly once
Indicated for the treatment of schizophrenia:
Initial dose:
50-75mg orally once a day
May titrate up or down dependent on the severity of symptoms and individual patient response; escalate to 100 mg daily in 3-4 days
Maintenance dose:
Mild: 5 to 15mg orally thrice a day
Moderate: 10 to 25mg orally thrice a day
Severe: 225mg/day orally when needed
Dose Adjustments
Start treatment at a lower dosage in aged and impaired individuals
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day orally twice or thrice a day
Immediate release
On day 1: 50 mg daily orally divided 2 times a day
On days 2 and 3: Dosage increased every day in the increments of 25-50 mg 2-3 times a day to 300-400 mg on day 4; additional modifications may be made in the increments of 25-50 mg 2 times a day at more than 2-day intervals.
Dosage: 150-750 mg daily
Extended release
On day 1: 300 mg daily orally; subsequently, the dose can be increased by up to 300 mg/day at more than one-day intervals.
400-800 mg daily for maintenance (monotherapy).
Patients who have been discontinued treatment for more than one week should reduce their dose upon start of therapy; patients who have been discontinued treatment for less than one week may restart at their past maintenance dose.
Initially, 20 mg orally 2 times a day with meals; may be enhanced to every other day when necessary; should not exceed more than 80 mg every 12 hours.
Assess the need for maintaining on a regular basis; clinical research has shown that dosages exceeding 20 mg every 12 hours provide no further benefit.
(associated with acute agitation):
Intramuscular: 10 mg every 2 hours or 20 mg every 4 hours; no more than 40 mg daily; use Intramuscular for up to 3 days, then switch to orally if needed.
Orally
Initial oral dosing of 10–15 mg/day; possible dosage increases of up to two weeks at every single dose strength; maximum oral dosing of 30 mg/day when given in tablet form; increased effectiveness above 15 mg/day not seen.
Abilify Maintena
First-time users of aripiprazole should start with 400 mg administered intramuscularly (IM) once monthly.
Before beginning therapy with Abilify Maintena, it is essential to determine whether you can take oral aripiprazole; this process may take up to two weeks.
After the initial injection, patients who have shown tolerance to aripiprazole should take 10 to 20 mg of the drug orally daily for 14 days.
Patients who are stable or tolerant to aripiprazole receive 400 mg intramuscularly (IM) once per month.
The monthly dose should be administered only 26 days after the previous injection. Consider reducing the monthly dose to 300 mg if an adverse reaction occurs.
Aristada Initio (single intramuscular dose)
Aristada is recommended for the initial treatment of schizophrenia when taken with oral aripiprazole.
Aristada may be started with a single dosage or restarted with a single dose when a dose was skipped.
Aristada Initio therapy should only be started if aripiprazole oral solution tolerance has been established; this may take up to 2 weeks.
aripiprazole orally (PO) should be tolerated before starting Aristada intramuscularly (IM).Aristada Initio 675 mg intramuscularly with aripiprazole 30 mg orally.
Do not take more than one dosage of Aristada Initio at a time. The first Aristada extended-release intramuscular injection may be administered on the exact same day as Aristada Initio or up to 10 days later.
Aristada (intramuscular monthly once )
Tolerance should be established with oral aripiprazole before starting Aristada; properly evaluating tolerance may take up to 2 weeks.
Aristada's first dosage should be based on the present aripiprazole oral dose; coadminister aripiprazole for 21 days orally
10 mg/day orally: Administer 441 mg intramuscularly once a month
15 mg/day orally: 662 mg intramuscular once a month or 882 mg intramuscular every six weeks, or 1064 mg intramuscular every two months
≥20 mg/day orally: 882 mg intramuscularly once monthly
Abilify Asimtufii (intramuscular every two months)
aripiprazole has never been used
Before starting 960 mg intramuscularly every two months, evaluate oral aripiprazole for tolerability. Tolerability testing may take up to 2 weeks. For 14 days following the first injection, individuals with known aripiprazole tolerance should continue taking oral aripiprazole (10 to 20 mg/day) or other antipsychotics orally.
With oral antipsychotics, Administer the initial dosage in combination with oral aripiprazole 10-20 mg orally for 14 consecutive days. Another oral antipsychotic that is stable (and is known to tolerate aripiprazole): For 14 days, provide the initial injection along with an oral antipsychotic.
Patients on Abilify Maintena In patients taking Abilify Maintena (one monthly dose)
Take Abilify Asimtufii 960 mg once every two months instead of the next scheduled injection of Abilify Maintena.
Provide the first injection of Abilify Asimtufii instead of the second or subsequent dose of Abilify Maintena.
If the 960-mg Abilify Asimtufii dose causes unpleasant responses, the dosage may be reduced to 720 mg once every two months. Abilify Asimtufii may be given up to 2 weeks before or after the 2-month prescribed time point.
Indicated for Schizophrenia
In hospitalization patients: 8-16 mg orally two-four times in a day
Should not exceed 64 mg in a day divided two-four times in a day
Out patients:4-8 mg orally three times in a day, decrease the dose to minimum effective dose
Nausea or vomiting
8-16 mg orally every day divided two-four times in a day
Should not exceed 24 mg
Intractable Hiccoughs as off-label
8-16 mg orally every day in divided two-three times in a day
Should not exceed 24 mg
Indicated for Schizophrenia
Oral dose
Initial dose: 10-50 mg orally two-three times in a day, may enhance everyday dose depending on the response, tolerability 10-20 mg increment every two-three days
General therapeutic dose:20-60 mg in a day
Should not generally exceed 100 mg in a day
Intramuscular dose (long-acting zuclopenthixol decanoate)
Before initiation, maintain tolerability with the oral tablet or with short-acting Intramuscular zuclopenthixol acetate
Maintenance dose: 150-300 mg every two-four weeks, may reach the dose upto 600 mg every one-four weeks for certain patients depending on the response, tolerability
Agitation or Aggression linked with schizophrenia/psychotic episodes
Oral dose
Initial dose: 10-50 mg orally two-three times in a day, may enhance everyday dose depending on the response, tolerability 10-20 mg increment every two-three days
General therapeutic dose:20-60 mg in a day
Should not generally exceed 100 mg in a day
Intramuscular dose (short-acting zuclopenthixol decanoate)
General dose: 50-150 mg as one dose, can repeat it every two-three days (certain patients might need another dose for 1-2 days following the initial dose and repeat it every two-three days as needed
Should not exceed 400 mg/ 4 injections throughout the treatment period
The treatment period, Should not exceed two weeks
Indicated for Schizophrenia
Initial dose: 30 mg orally for one day, one dose of 675 mg of nanocrystal dispersion with the 1st dose of the aripiprazole lauroxil depending on ongoing aripiprazole dose with/within ten days following administering 675 mg dose
Or
21-day orally overlap: Administer aripiprazole orally for 21 days combined with 1st dose of the aripiprazole lauroxil depending on the ongoing aripiprazole dose
Turning of aripiprazole oral form to intramuscular aripiprazole lauroxil (i.e.,Aristada)
aripiprazole orally 10 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e.,Aristada) dose: 441 mg for a month
aripiprazole orally 15 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e., Aristada) dose: 662 mg for a month or 882 mg every six weeks or 1064 mg every two months
aripiprazole orally >20 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e.,Aristada) dose: 882 mg for a month
Note:
Dose adjustment: Modify aripiprazole lauroxil dose as per requirement; if the dose is needed before then, the recommended interval, Should not administer <14 days following the earlier injection
20-40 mg orally each day
Increase by 20 mg if required
Keep the lowest maintenance dose
Do not increase the dose to more than 60 mg each day
Apply a dose of 3.8 mg/24 hours patch initially, then increase to 5.7 mg/24 hours or 7.6 mg/24 hours after one week.
Dose Adjustments
Dosage Modifications
Hepatic impairment
Child-Pugh score A or B (Mild-to-moderate): dose adjustment is not required
Child-Pugh score C (Severe): Contraindicated
Renal impairment
Mild-severe (GFR 15 to 90 mL/min): dose adjustment is not required
Dialysis patients: Not studied
There are no studies on effect of renal function and the excretion of various other metabolites.
Indicated for Schizophrenia
42 mg orally every day
The titration of the dose is typically not required
Bipolar Disorder
42 mg orally every day
The titration of the dose is typically not required
It is used for depressive episodes with bipolar I or bipolar II disorders in elderly patients, as adjunctive therapy with valproate or lithium, or as monotherapy
Note:
Coadministration with the CYP3A4 inhibitors
Strong: Diminish the dose to 10.5 mg every day
Moderate: Diminish the dose to 21 mg every day
Hepatic impairment
Moderate-severe: 21mg orally every day
Indicated for schizophrenic patients associated with symptoms of depression
50 mg/8 mg orally 2-3 times daily
Provide a fourth dose at bedtime if required
Maintenance dose- 2 mg/25 mg or 4 mg/ 25 mg orally 2-4 times daily
10 mg/2 mg and 10 mg/4 mg can increase the maintenance dose flexibility
Do not exceed the dose of more than 200 mg/16 mg
and Biploar I agitation :
10 mg inhaled orally once within a period 24-hours
should be administered by healthcare professional only
Take a dose of 12.5 mg orally one time a day; raise the dose up to 25 to 50 mg daily and if well tolerated
To achieve target dose of daily 300 to 450 mg is administered in divided doses by completion of two weeks
It may raise dose one or two times in week up to 100 mg and a daily dose not more than 900 mg
Dosage Modifications
For Coadministration with CYP inhibitors
Strong CYP1A2 inhibitors: Use one-third part of clozapine dose
Moderate or weak CYP1A2 inhibitors: decrease clozapine dose if required
CYP2D6 or CYP3A4 inhibitors: decrease clozapine dose if required
CYP2D6 poor metabolizers: decrease clozapine dose if required
For Coadministration with CYP inducers
Strong CYP3A4 inducers: Coadministration not suggested
Moderate or weak CYP1A2 or CYP3A4 inducers: increase clozapine dose if required
For Renal or hepatic impairment
Decreased dose may be required
Dosing Considerations
Before starting, obtain complete blood count with differential for initial absolute neutrophil count to maintain therapy, absolute neutrophil count must be regularly monitored
Mild/moderate
120 mcg Sublingual or buccal initially
If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe
180 mcg Sublingual or buccal initially
If the agitation continues, administer 90 mcg in two doses at least 2 hours apart; do not exceed more than 360 mcg/day
Dose Adjustments
Dosage Modifications
Intravenous:
Consider lowering the dosage in individuals with hepatic impairment and those over 65 yrs of age; clearance declines with increasing severity of the hepatic impairment
Renal impairment: Dose adjustment is not required
Sublingual or buccal:
Renal impairment
dose adjustment is not necessary
Hepatic impairment
Mild/moderate (Child-Pugh score A or B)
Mild/moderate agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Severe agitation: 120 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe (Child-Pugh score C)
Mild/moderate agitation: 60 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 180 mcg/day
Severe agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
A dose of 30-45 mg (2-3 tablets) 3 to 4 times a day. the daily dose should not exceed more than 600 mg
Take a dose of 400 mg to 2.4 g daily in 2 to 4 divided doses
Initially, 2 mg weekly through deep intramuscular injection. The dose may be increased based on the patient's response. Maintenance dose: 1-10 mg weekly.
Administer an initial dose of 25 mg intramuscularly as test dose followed by 25 to 50 mg after 4 to 7 days
Administer a maintenance dose of 50 to 100 mg intramuscularly in every 4 weeks
Maximum dose should not be more than 200 mg in every 4 weeks
Initially, administer 75 mg per day in the divided dosages, following may increase doses about 25 mg daily in weekly intervals till the optimum effect is attained. Maximum dose: 300 mg per day
Dose Adjustments
Dose modifications Renal impairment: Its use is Contraindicated Hepatic impairment: Its use is Contraindicated
0.25 - 1
mg
every 12 hrs
5 - 7
days
<13 years: Safety and efficacy not established
Day 1-4: 0.5 mg orally every day
Day 5-7: Adjust dosage to 1 mg every day
Day 8: Adjust to 2 mg/day
Do not exceed 4 mg/day
<13 years: Safety and efficacy not established
>13 years:
Initial dose: 0.5mg/day orally in the morning or evening
Titration dose: may increase 0.5mg to 1mg/day at 24 hours intervals
Maintenance dose:3mg orally per day
Maximum dose: 6mg orally per day
<12 years:
Safety and efficacy not established
>12 years:
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day
<12 years:
Safety and efficacy not established
>12 years:
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day
Below 12 years
Safety and efficacy were not established
Above 12 years (immediate release, monotherapy,)
Day 1: 50 mg daily orally divided 2 times a day
Day 2: 100 mg daily orally divided 2 times a day
Day 3: 200 mg daily orally divided 2 times a day
Day 4: 300 mg daily orally divided 2 times a day
Day 5: 400 mg daily orally divided 2 times a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-800 mg daily
Depending on tolerance and response, the daily dose can be divided 3 times a day
Above 12 yrs (extended release, monotherapy)
Day 1: 50 mg orally once a day
Day 2: 100 mg orally once a day
Day 3: 200 mg orally once a day
Day 4: 300 mg orally once a day
Day 5: 400 mg orally once a day; further dose modifications should be less than 100 mg daily in increments
Mania, Bipolar I Disorder
Below 10 yrs
Safety and efficacy were not established
Above 10 years (immediate release,monotherapy)
Day 1: 50 mg daily orally divided 2 times a day
Day 2: 100 mg daily orally divided 2 times a day
Day 3: 200 mg daily orally divided 2 times a day
Day 4: 300 mg daily orally divided 2 times a day
Day 5: 400 mg daily orally divided 2 times a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-600 mg daily
Depending on tolerance and response, the daily dose can be divided 3 times a day
Above 10 years (extended release, monotherapy)
Day 1: 50 mg orally once a day
Day 2: 100 mg orally once a day
Day 3: 200 mg orally once a day
Day 4: 300 mg orally once a day
Day 5: 400 mg orally once a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-600 mg daily once
<13 years: Safety and efficacy not established
13 to 17 years: Initial oral dosage of 2 mg/day, followed by a rise to 5 mg/day after two days, and then, after an additional two days, a possible increase to the recommended dose of 10 mg/day;
maintenance dose: 10 to 30 mg/day
Indicated for Schizophrenia
Age >12 years
In hospitalization patients: 8-16 mg orally two-four times in a day
Should not exceed 64 mg in a day divided two-four times in a day
Out patients:4-8 mg orally three times in a day, decrease the dose to minimum effective dose
Age <12 years
Safety and efficacy not established
Intractable Hiccoughs as off-label
Age >12 years
8-16 mg orally every day in divided two-three times in a day
Should not exceed 24 mg
Age <12 years
Safety and efficacy not established
A pharmacokinetic study among elderly patients with asenapine SL found that dosage adjustments based only on age are not recommended.
Exposure is 30-40% more in elderly patients than in adults.
Not recommended for dementia-related psychosis.
May have an increased risk of mortality in elderly patients suffering from dementia-related psychosis.
for children above 6 years, a dose of 15 to 30 mg (1-2 tablets) 3 to 4 times a day
Above 1 year weighing around 10 kg: Initially, administer 500 mcg, may increase by 1 mg every additional 5 kg of the body weight. Maximum dose: 10 mg/day. Dose according to the response. Maintenance dose: not to exceed twice of initial dose; above 12 years: Same as the adult dose
Dose Adjustments
Dose modifications
Renal impairment:
Its use is Contraindicated
Hepatic impairment:
Its use is Contraindicated
0.25 - 0.5
mg
Tablet
Orally
every 8 hrs
Orally
Initially:0.5mg/day
At an interval of 24 hours, may increase the dose from 1-2mg/day
Maintenance dose:2 to 8mg orally/day
Maximum dose:16mg orally/day
Intramuscular
Initial dose:25mg intramuscular every two weeks
Titration dose: may increase up to 37.5mg or 50mg
Maximum dose: 50mg intramuscular every two weeks
In depression due to schizophrenia, if extremely required, start with the lowest dose, like 1 tablet 3-4 times daily
Mild/moderate
120 mcg Sublingual or buccal initially
If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Dose Adjustments
Dosage Modifications
Intravenous:
Consider lowering the dosage in individuals with hepatic impairment and those over 65 yrs of age; clearance declines with increasing severity of the hepatic impairment
Renal impairment: Dose adjustment is not required
Sublingual or buccal:
Renal impairment
dose adjustment is not necessary
Hepatic impairment
Mild/moderate (Child-Pugh score A or B)
Mild/moderate agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Severe agitation: 120 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe (Child-Pugh score C)
Mild/moderate agitation: 60 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 180 mcg/day
Severe agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Elderly patients, a dose of 15 to 30 mg (1-2 tablets) 3 to 4 times a day
Initially, 15 to 30 mg per day in the divided dosages. May increase the dose if required according to the patient’s tolerability
Dose Adjustments
Dose modifications
Renal impairment: Its use is Contraindicated
Hepatic impairment: Its use is Contraindicated
Future Trends
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914490/
https://www.ncbi.nlm.nih.gov/books/NBK539864/
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» Home » CAD » Psychiatry » Psychiatry Disorder » Schizophrenia
Schizophrenia is a mental disorder characterized by delusions, hallucinations (auditory or visual), and disturbances in thought, perception, behavior, and emotional responses.
Although the course of the disease varies from individual to individual, it is usually persistent and disabling.
It is detected in the late teen years to early thirties. The disease’s negative symptoms (Classic 5 A’s) are Affect (blunted), Alogia, Asociality, Avolition, and Anhedonia.
The prevalence of schizophrenia is relatively high with early onset in adulthood and develops into a chronic condition. The prevalence varies globally, from 0.6 to 1.9% in the United States, affecting about 1% of the adult population.
Males are slightly affected more and have an early onset of the disease than females with a ratio of 4: 1. A 40% risk is estimated between the use of cannabis, cocaine, and schizophrenia.
Schizophrenia is mainly attributed to increased dopamine transmission in the brain’s mesolimbic pathway. In contrast, low dopamine levels in the nigrostriatal pathway are hypothesized to generate motor symptoms via an effect on the extrapyramidal system. Low levels of mesocortical dopamine are believed to induce the disease’s negative symptoms.
High prolactin levels cause other symptoms like decreased libido and amenorrhea due to the declined availability of tuberoinfundibular dopamine. Though serotonergic hyperactivity has been demonstrated to have a role in the development of schizophrenia, evidence suggests that glutaminergic hypoactivity is also involved.
NMDA receptor antagonists have been proven to exacerbate both positive and negative symptoms in schizophrenia. Schizophrenia results in a decrease in grey matter volume that affects both the parietal and temporal lobes. There are also alterations in the hippocampus and frontal lobes, which may be a factor in memory and cognitive impairments.
Several theories postulate that abnormalities in neurotransmitters, such as glutaminergic and GABA hypoactivity or dopaminergic, serotonergic, and alpha-adrenergic hyperactivity, contribute to the development of schizophrenia. The gene neuregulin (NGR1) is involved in glutamate signaling and brain development.
Dysbindin (DTNBP1) promotes glutamate release, and catecholamine O-methyl transferase (COMT) polymorphism modulates dopamine function. Maternal malnutrition and vitamin D deficiency, pre-eclampsia, perinatal hypoxia, gestational diabetes, complications during birth, abnormal fetal development, and low birth weight increase the risk of developing this disease.
A positive family history of schizophrenia in a first-degree relative has a 6.5% risk of transmission and the risk is increased in twins to more than 40%. Both parents with schizophrenia have a 60% risk of offspring being affected.
The prognosis of the condition depends on several factors like age of onset, cognitive impairment, and co-morbid conditions. Suicide is the prime reason for premature mortality, and most patients report suicidal ideation. The estimated suicide rate is 4.9% in patients who lose their life from schizophrenia; it is observed in the early stage of the disease.
Clinical History
Schizophrenia typically begins to manifest in late adolescence or early adulthood. The patient may experience a gradual onset of symptoms or a sudden behavior change. Common initial symptoms include social withdrawal, decline in academic or occupational performance, increased irritability or agitation, and changes in sleep patterns.
Positive symptoms refer to the presence of abnormal experiences or behaviors that are not typically seen in healthy individuals. These symptoms may include:
Negative symptoms involve a loss or decrease in normal functioning or experiences. These symptoms may include:
Schizophrenia can also affect cognitive functioning, leading to problems with attention, memory, and executive functions (such as planning and decision-making). These cognitive impairments can significantly impact daily functioning and overall quality of life.
The symptoms of schizophrenia are chronic and can last for at least six months. The severity and duration of symptoms may vary over time, with periods of exacerbation and remission. The condition can significantly impact the patient’s relationships, education, employment, and overall functioning.
Physical Examination
Schizophrenia is primarily a mental disorder, and its diagnosis is based on the presence of characteristic symptoms rather than physical findings. However, certain physical findings may be observed in individuals with schizophrenia, either as direct consequences of the illness or due to associated factors.
Motor Abnormalities:
Some individuals with schizophrenia may exhibit motor abnormalities, such as:
Motoric immobility: A decrease in spontaneous movement or voluntary actions.
Weight Changes: Schizophrenia can be associated with weight changes due to various factors, including side effects of antipsychotic medications or alterations in appetite and metabolism.
Movement Disorders: In some cases, individuals with schizophrenia may develop movement disorders, such as:
Self-neglect: In severe cases or during periods of active symptoms, individuals with schizophrenia may neglect their personal hygiene, appearance, and self-care, which can lead to physical signs like poor grooming, unkempt hair, and dirty clothing.
Differential Diagnoses
Delusional Disorder
Pervasive developmental disorder
Substance-induced psychotic disorder
Paranoid personality disorder
Schizotypal personality disorder
In the initial treatment of acute psychosis, it is recommended to begin with an oral second-generation antipsychotic medication. Examples of these medications include olanzapine, aripiprazole, risperidone, asenapine, quetiapine, lurasidone, sertindole, brexpiprazole, ziprasidone, molindone, iloperidone, and others.
In some instances, if clinically necessary, a benzodiazepine such as clonazepam, diazepam, or lorazepam may be prescribed alongside the antipsychotic to manage behavioral disturbances and non-acute anxiety.
While first-generation antipsychotics (FGA) like flupentixol, trifluoperazine, fluphenazine, pimozide, haloperidol, sulpiride, chlorpromazine, and others are not commonly used as first-line treatment, they can still be utilized if needed.
Cognitive behavioral therapy (CBT) and art and drama therapies can be beneficial in addressing the disease’s negative symptoms, improving insight, and preventing relapse. These approaches aim to counteract the negative impact of the disease and assist in the patient’s rehabilitation process.
Clozapine is reserved for cases of treatment resistance, with a poor response to at least two different antipsychotic medications. It requires close monitoring, including weekly blood tests for the first six months, biweekly tests for the following six months, and monthly tests to monitor the white blood cell count due to the risk of agranulocytosis.
During the maintenance phase of treatment, prophylaxis and rehabilitation efforts play a vital role in reintegrating patients into the community. It is important to establish the minimum effective dose of antipsychotics during this period.
Substance abuse is common among patients with schizophrenia and can worsen both positive and negative symptoms. Therefore, psychosocial and pharmacotherapeutic approaches should be employed to address substance misuse. In cases of extensive and persistent substance misuse, clozapine may be considered.
0.5 - 5
mg
every 8 hrs
do not exceed the dose of more than 30 mg/day
5
mg
sublingually
every 12 hrs
a day; maybe increase to 10 mg sublingually 2 times a day
Do not exceed 20 mg per day
Day 1-4: 1mg orally every day
Day 5-7: Adjust dosage to 2 mg every day
Day 8: Adjust to 4mg/day
Do not exceed 4mg/day
Orally
Initially:2mg/day
At an interval of 24 hours, may increase the dose from 1-2mg/day
Maintenance dose:2 to 8mg orally/day
Maximum dose:16mg orally/day
Intramuscular
Initial dose:25mg intramuscular every two weeks
Titration dose: may increase up to 37.5mg or 50mg
Maximum dose: 50mg intramuscular every two weeks
Subcutaneous
90mg or 120mg subcutaneously monthly once
Indicated for the treatment of schizophrenia:
Initial dose:
50-75mg orally once a day
May titrate up or down dependent on the severity of symptoms and individual patient response; escalate to 100 mg daily in 3-4 days
Maintenance dose:
Mild: 5 to 15mg orally thrice a day
Moderate: 10 to 25mg orally thrice a day
Severe: 225mg/day orally when needed
Dose Adjustments
Start treatment at a lower dosage in aged and impaired individuals
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day orally twice or thrice a day
Immediate release
On day 1: 50 mg daily orally divided 2 times a day
On days 2 and 3: Dosage increased every day in the increments of 25-50 mg 2-3 times a day to 300-400 mg on day 4; additional modifications may be made in the increments of 25-50 mg 2 times a day at more than 2-day intervals.
Dosage: 150-750 mg daily
Extended release
On day 1: 300 mg daily orally; subsequently, the dose can be increased by up to 300 mg/day at more than one-day intervals.
400-800 mg daily for maintenance (monotherapy).
Patients who have been discontinued treatment for more than one week should reduce their dose upon start of therapy; patients who have been discontinued treatment for less than one week may restart at their past maintenance dose.
Initially, 20 mg orally 2 times a day with meals; may be enhanced to every other day when necessary; should not exceed more than 80 mg every 12 hours.
Assess the need for maintaining on a regular basis; clinical research has shown that dosages exceeding 20 mg every 12 hours provide no further benefit.
(associated with acute agitation):
Intramuscular: 10 mg every 2 hours or 20 mg every 4 hours; no more than 40 mg daily; use Intramuscular for up to 3 days, then switch to orally if needed.
Orally
Initial oral dosing of 10–15 mg/day; possible dosage increases of up to two weeks at every single dose strength; maximum oral dosing of 30 mg/day when given in tablet form; increased effectiveness above 15 mg/day not seen.
Abilify Maintena
First-time users of aripiprazole should start with 400 mg administered intramuscularly (IM) once monthly.
Before beginning therapy with Abilify Maintena, it is essential to determine whether you can take oral aripiprazole; this process may take up to two weeks.
After the initial injection, patients who have shown tolerance to aripiprazole should take 10 to 20 mg of the drug orally daily for 14 days.
Patients who are stable or tolerant to aripiprazole receive 400 mg intramuscularly (IM) once per month.
The monthly dose should be administered only 26 days after the previous injection. Consider reducing the monthly dose to 300 mg if an adverse reaction occurs.
Aristada Initio (single intramuscular dose)
Aristada is recommended for the initial treatment of schizophrenia when taken with oral aripiprazole.
Aristada may be started with a single dosage or restarted with a single dose when a dose was skipped.
Aristada Initio therapy should only be started if aripiprazole oral solution tolerance has been established; this may take up to 2 weeks.
aripiprazole orally (PO) should be tolerated before starting Aristada intramuscularly (IM).Aristada Initio 675 mg intramuscularly with aripiprazole 30 mg orally.
Do not take more than one dosage of Aristada Initio at a time. The first Aristada extended-release intramuscular injection may be administered on the exact same day as Aristada Initio or up to 10 days later.
Aristada (intramuscular monthly once )
Tolerance should be established with oral aripiprazole before starting Aristada; properly evaluating tolerance may take up to 2 weeks.
Aristada's first dosage should be based on the present aripiprazole oral dose; coadminister aripiprazole for 21 days orally
10 mg/day orally: Administer 441 mg intramuscularly once a month
15 mg/day orally: 662 mg intramuscular once a month or 882 mg intramuscular every six weeks, or 1064 mg intramuscular every two months
≥20 mg/day orally: 882 mg intramuscularly once monthly
Abilify Asimtufii (intramuscular every two months)
aripiprazole has never been used
Before starting 960 mg intramuscularly every two months, evaluate oral aripiprazole for tolerability. Tolerability testing may take up to 2 weeks. For 14 days following the first injection, individuals with known aripiprazole tolerance should continue taking oral aripiprazole (10 to 20 mg/day) or other antipsychotics orally.
With oral antipsychotics, Administer the initial dosage in combination with oral aripiprazole 10-20 mg orally for 14 consecutive days. Another oral antipsychotic that is stable (and is known to tolerate aripiprazole): For 14 days, provide the initial injection along with an oral antipsychotic.
Patients on Abilify Maintena In patients taking Abilify Maintena (one monthly dose)
Take Abilify Asimtufii 960 mg once every two months instead of the next scheduled injection of Abilify Maintena.
Provide the first injection of Abilify Asimtufii instead of the second or subsequent dose of Abilify Maintena.
If the 960-mg Abilify Asimtufii dose causes unpleasant responses, the dosage may be reduced to 720 mg once every two months. Abilify Asimtufii may be given up to 2 weeks before or after the 2-month prescribed time point.
Indicated for Schizophrenia
In hospitalization patients: 8-16 mg orally two-four times in a day
Should not exceed 64 mg in a day divided two-four times in a day
Out patients:4-8 mg orally three times in a day, decrease the dose to minimum effective dose
Nausea or vomiting
8-16 mg orally every day divided two-four times in a day
Should not exceed 24 mg
Intractable Hiccoughs as off-label
8-16 mg orally every day in divided two-three times in a day
Should not exceed 24 mg
Indicated for Schizophrenia
Oral dose
Initial dose: 10-50 mg orally two-three times in a day, may enhance everyday dose depending on the response, tolerability 10-20 mg increment every two-three days
General therapeutic dose:20-60 mg in a day
Should not generally exceed 100 mg in a day
Intramuscular dose (long-acting zuclopenthixol decanoate)
Before initiation, maintain tolerability with the oral tablet or with short-acting Intramuscular zuclopenthixol acetate
Maintenance dose: 150-300 mg every two-four weeks, may reach the dose upto 600 mg every one-four weeks for certain patients depending on the response, tolerability
Agitation or Aggression linked with schizophrenia/psychotic episodes
Oral dose
Initial dose: 10-50 mg orally two-three times in a day, may enhance everyday dose depending on the response, tolerability 10-20 mg increment every two-three days
General therapeutic dose:20-60 mg in a day
Should not generally exceed 100 mg in a day
Intramuscular dose (short-acting zuclopenthixol decanoate)
General dose: 50-150 mg as one dose, can repeat it every two-three days (certain patients might need another dose for 1-2 days following the initial dose and repeat it every two-three days as needed
Should not exceed 400 mg/ 4 injections throughout the treatment period
The treatment period, Should not exceed two weeks
Indicated for Schizophrenia
Initial dose: 30 mg orally for one day, one dose of 675 mg of nanocrystal dispersion with the 1st dose of the aripiprazole lauroxil depending on ongoing aripiprazole dose with/within ten days following administering 675 mg dose
Or
21-day orally overlap: Administer aripiprazole orally for 21 days combined with 1st dose of the aripiprazole lauroxil depending on the ongoing aripiprazole dose
Turning of aripiprazole oral form to intramuscular aripiprazole lauroxil (i.e.,Aristada)
aripiprazole orally 10 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e.,Aristada) dose: 441 mg for a month
aripiprazole orally 15 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e., Aristada) dose: 662 mg for a month or 882 mg every six weeks or 1064 mg every two months
aripiprazole orally >20 mg in a day: Initial intramuscular aripiprazole lauroxil (i.e.,Aristada) dose: 882 mg for a month
Note:
Dose adjustment: Modify aripiprazole lauroxil dose as per requirement; if the dose is needed before then, the recommended interval, Should not administer <14 days following the earlier injection
20-40 mg orally each day
Increase by 20 mg if required
Keep the lowest maintenance dose
Do not increase the dose to more than 60 mg each day
Apply a dose of 3.8 mg/24 hours patch initially, then increase to 5.7 mg/24 hours or 7.6 mg/24 hours after one week.
Dose Adjustments
Dosage Modifications
Hepatic impairment
Child-Pugh score A or B (Mild-to-moderate): dose adjustment is not required
Child-Pugh score C (Severe): Contraindicated
Renal impairment
Mild-severe (GFR 15 to 90 mL/min): dose adjustment is not required
Dialysis patients: Not studied
There are no studies on effect of renal function and the excretion of various other metabolites.
Indicated for Schizophrenia
42 mg orally every day
The titration of the dose is typically not required
Bipolar Disorder
42 mg orally every day
The titration of the dose is typically not required
It is used for depressive episodes with bipolar I or bipolar II disorders in elderly patients, as adjunctive therapy with valproate or lithium, or as monotherapy
Note:
Coadministration with the CYP3A4 inhibitors
Strong: Diminish the dose to 10.5 mg every day
Moderate: Diminish the dose to 21 mg every day
Hepatic impairment
Moderate-severe: 21mg orally every day
Indicated for schizophrenic patients associated with symptoms of depression
50 mg/8 mg orally 2-3 times daily
Provide a fourth dose at bedtime if required
Maintenance dose- 2 mg/25 mg or 4 mg/ 25 mg orally 2-4 times daily
10 mg/2 mg and 10 mg/4 mg can increase the maintenance dose flexibility
Do not exceed the dose of more than 200 mg/16 mg
and Biploar I agitation :
10 mg inhaled orally once within a period 24-hours
should be administered by healthcare professional only
Take a dose of 12.5 mg orally one time a day; raise the dose up to 25 to 50 mg daily and if well tolerated
To achieve target dose of daily 300 to 450 mg is administered in divided doses by completion of two weeks
It may raise dose one or two times in week up to 100 mg and a daily dose not more than 900 mg
Dosage Modifications
For Coadministration with CYP inhibitors
Strong CYP1A2 inhibitors: Use one-third part of clozapine dose
Moderate or weak CYP1A2 inhibitors: decrease clozapine dose if required
CYP2D6 or CYP3A4 inhibitors: decrease clozapine dose if required
CYP2D6 poor metabolizers: decrease clozapine dose if required
For Coadministration with CYP inducers
Strong CYP3A4 inducers: Coadministration not suggested
Moderate or weak CYP1A2 or CYP3A4 inducers: increase clozapine dose if required
For Renal or hepatic impairment
Decreased dose may be required
Dosing Considerations
Before starting, obtain complete blood count with differential for initial absolute neutrophil count to maintain therapy, absolute neutrophil count must be regularly monitored
Mild/moderate
120 mcg Sublingual or buccal initially
If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe
180 mcg Sublingual or buccal initially
If the agitation continues, administer 90 mcg in two doses at least 2 hours apart; do not exceed more than 360 mcg/day
Dose Adjustments
Dosage Modifications
Intravenous:
Consider lowering the dosage in individuals with hepatic impairment and those over 65 yrs of age; clearance declines with increasing severity of the hepatic impairment
Renal impairment: Dose adjustment is not required
Sublingual or buccal:
Renal impairment
dose adjustment is not necessary
Hepatic impairment
Mild/moderate (Child-Pugh score A or B)
Mild/moderate agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Severe agitation: 120 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe (Child-Pugh score C)
Mild/moderate agitation: 60 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 180 mcg/day
Severe agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
A dose of 30-45 mg (2-3 tablets) 3 to 4 times a day. the daily dose should not exceed more than 600 mg
Take a dose of 400 mg to 2.4 g daily in 2 to 4 divided doses
Initially, 2 mg weekly through deep intramuscular injection. The dose may be increased based on the patient's response. Maintenance dose: 1-10 mg weekly.
Administer an initial dose of 25 mg intramuscularly as test dose followed by 25 to 50 mg after 4 to 7 days
Administer a maintenance dose of 50 to 100 mg intramuscularly in every 4 weeks
Maximum dose should not be more than 200 mg in every 4 weeks
Initially, administer 75 mg per day in the divided dosages, following may increase doses about 25 mg daily in weekly intervals till the optimum effect is attained. Maximum dose: 300 mg per day
Dose Adjustments
Dose modifications Renal impairment: Its use is Contraindicated Hepatic impairment: Its use is Contraindicated
0.25 - 1
mg
every 12 hrs
5 - 7
days
<13 years: Safety and efficacy not established
Day 1-4: 0.5 mg orally every day
Day 5-7: Adjust dosage to 1 mg every day
Day 8: Adjust to 2 mg/day
Do not exceed 4 mg/day
<13 years: Safety and efficacy not established
>13 years:
Initial dose: 0.5mg/day orally in the morning or evening
Titration dose: may increase 0.5mg to 1mg/day at 24 hours intervals
Maintenance dose:3mg orally per day
Maximum dose: 6mg orally per day
<12 years:
Safety and efficacy not established
>12 years:
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day
<12 years:
Safety and efficacy not established
>12 years:
Mild to Moderate:
Initial dose-2 mg orally thrice a day
Maintenance dose-15 mg per day orally once
Severe:
Initial dose-5 mg orally twice a day
Maintenance dose-20 to 30 mg per day orally once
Do not exceed 60 mg per day
Below 12 years
Safety and efficacy were not established
Above 12 years (immediate release, monotherapy,)
Day 1: 50 mg daily orally divided 2 times a day
Day 2: 100 mg daily orally divided 2 times a day
Day 3: 200 mg daily orally divided 2 times a day
Day 4: 300 mg daily orally divided 2 times a day
Day 5: 400 mg daily orally divided 2 times a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-800 mg daily
Depending on tolerance and response, the daily dose can be divided 3 times a day
Above 12 yrs (extended release, monotherapy)
Day 1: 50 mg orally once a day
Day 2: 100 mg orally once a day
Day 3: 200 mg orally once a day
Day 4: 300 mg orally once a day
Day 5: 400 mg orally once a day; further dose modifications should be less than 100 mg daily in increments
Mania, Bipolar I Disorder
Below 10 yrs
Safety and efficacy were not established
Above 10 years (immediate release,monotherapy)
Day 1: 50 mg daily orally divided 2 times a day
Day 2: 100 mg daily orally divided 2 times a day
Day 3: 200 mg daily orally divided 2 times a day
Day 4: 300 mg daily orally divided 2 times a day
Day 5: 400 mg daily orally divided 2 times a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-600 mg daily
Depending on tolerance and response, the daily dose can be divided 3 times a day
Above 10 years (extended release, monotherapy)
Day 1: 50 mg orally once a day
Day 2: 100 mg orally once a day
Day 3: 200 mg orally once a day
Day 4: 300 mg orally once a day
Day 5: 400 mg orally once a day; further dose modifications should be less than 100 mg daily in increments
Dosage: 400-600 mg daily once
<13 years: Safety and efficacy not established
13 to 17 years: Initial oral dosage of 2 mg/day, followed by a rise to 5 mg/day after two days, and then, after an additional two days, a possible increase to the recommended dose of 10 mg/day;
maintenance dose: 10 to 30 mg/day
Indicated for Schizophrenia
Age >12 years
In hospitalization patients: 8-16 mg orally two-four times in a day
Should not exceed 64 mg in a day divided two-four times in a day
Out patients:4-8 mg orally three times in a day, decrease the dose to minimum effective dose
Age <12 years
Safety and efficacy not established
Intractable Hiccoughs as off-label
Age >12 years
8-16 mg orally every day in divided two-three times in a day
Should not exceed 24 mg
Age <12 years
Safety and efficacy not established
A pharmacokinetic study among elderly patients with asenapine SL found that dosage adjustments based only on age are not recommended.
Exposure is 30-40% more in elderly patients than in adults.
Not recommended for dementia-related psychosis.
May have an increased risk of mortality in elderly patients suffering from dementia-related psychosis.
for children above 6 years, a dose of 15 to 30 mg (1-2 tablets) 3 to 4 times a day
Above 1 year weighing around 10 kg: Initially, administer 500 mcg, may increase by 1 mg every additional 5 kg of the body weight. Maximum dose: 10 mg/day. Dose according to the response. Maintenance dose: not to exceed twice of initial dose; above 12 years: Same as the adult dose
Dose Adjustments
Dose modifications
Renal impairment:
Its use is Contraindicated
Hepatic impairment:
Its use is Contraindicated
0.25 - 0.5
mg
Tablet
Orally
every 8 hrs
Orally
Initially:0.5mg/day
At an interval of 24 hours, may increase the dose from 1-2mg/day
Maintenance dose:2 to 8mg orally/day
Maximum dose:16mg orally/day
Intramuscular
Initial dose:25mg intramuscular every two weeks
Titration dose: may increase up to 37.5mg or 50mg
Maximum dose: 50mg intramuscular every two weeks
In depression due to schizophrenia, if extremely required, start with the lowest dose, like 1 tablet 3-4 times daily
Mild/moderate
120 mcg Sublingual or buccal initially
If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Dose Adjustments
Dosage Modifications
Intravenous:
Consider lowering the dosage in individuals with hepatic impairment and those over 65 yrs of age; clearance declines with increasing severity of the hepatic impairment
Renal impairment: Dose adjustment is not required
Sublingual or buccal:
Renal impairment
dose adjustment is not necessary
Hepatic impairment
Mild/moderate (Child-Pugh score A or B)
Mild/moderate agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Severe agitation: 120 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 240 mcg/day
Severe (Child-Pugh score C)
Mild/moderate agitation: 60 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 180 mcg/day
Severe agitation: 90 mcg Sublingual initially; If the agitation continues, administer 60 mcg in two doses at least 2 hours apart; do not exceed more than 210 mcg/day
Elderly patients, a dose of 15 to 30 mg (1-2 tablets) 3 to 4 times a day
Initially, 15 to 30 mg per day in the divided dosages. May increase the dose if required according to the patient’s tolerability
Dose Adjustments
Dose modifications
Renal impairment: Its use is Contraindicated
Hepatic impairment: Its use is Contraindicated
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914490/
https://www.ncbi.nlm.nih.gov/books/NBK539864/
Schizophrenia is a mental disorder characterized by delusions, hallucinations (auditory or visual), and disturbances in thought, perception, behavior, and emotional responses.
Although the course of the disease varies from individual to individual, it is usually persistent and disabling.
It is detected in the late teen years to early thirties. The disease’s negative symptoms (Classic 5 A’s) are Affect (blunted), Alogia, Asociality, Avolition, and Anhedonia.
The prevalence of schizophrenia is relatively high with early onset in adulthood and develops into a chronic condition. The prevalence varies globally, from 0.6 to 1.9% in the United States, affecting about 1% of the adult population.
Males are slightly affected more and have an early onset of the disease than females with a ratio of 4: 1. A 40% risk is estimated between the use of cannabis, cocaine, and schizophrenia.
Schizophrenia is mainly attributed to increased dopamine transmission in the brain’s mesolimbic pathway. In contrast, low dopamine levels in the nigrostriatal pathway are hypothesized to generate motor symptoms via an effect on the extrapyramidal system. Low levels of mesocortical dopamine are believed to induce the disease’s negative symptoms.
High prolactin levels cause other symptoms like decreased libido and amenorrhea due to the declined availability of tuberoinfundibular dopamine. Though serotonergic hyperactivity has been demonstrated to have a role in the development of schizophrenia, evidence suggests that glutaminergic hypoactivity is also involved.
NMDA receptor antagonists have been proven to exacerbate both positive and negative symptoms in schizophrenia. Schizophrenia results in a decrease in grey matter volume that affects both the parietal and temporal lobes. There are also alterations in the hippocampus and frontal lobes, which may be a factor in memory and cognitive impairments.
Several theories postulate that abnormalities in neurotransmitters, such as glutaminergic and GABA hypoactivity or dopaminergic, serotonergic, and alpha-adrenergic hyperactivity, contribute to the development of schizophrenia. The gene neuregulin (NGR1) is involved in glutamate signaling and brain development.
Dysbindin (DTNBP1) promotes glutamate release, and catecholamine O-methyl transferase (COMT) polymorphism modulates dopamine function. Maternal malnutrition and vitamin D deficiency, pre-eclampsia, perinatal hypoxia, gestational diabetes, complications during birth, abnormal fetal development, and low birth weight increase the risk of developing this disease.
A positive family history of schizophrenia in a first-degree relative has a 6.5% risk of transmission and the risk is increased in twins to more than 40%. Both parents with schizophrenia have a 60% risk of offspring being affected.
The prognosis of the condition depends on several factors like age of onset, cognitive impairment, and co-morbid conditions. Suicide is the prime reason for premature mortality, and most patients report suicidal ideation. The estimated suicide rate is 4.9% in patients who lose their life from schizophrenia; it is observed in the early stage of the disease.
Clinical History
Schizophrenia typically begins to manifest in late adolescence or early adulthood. The patient may experience a gradual onset of symptoms or a sudden behavior change. Common initial symptoms include social withdrawal, decline in academic or occupational performance, increased irritability or agitation, and changes in sleep patterns.
Positive symptoms refer to the presence of abnormal experiences or behaviors that are not typically seen in healthy individuals. These symptoms may include:
Negative symptoms involve a loss or decrease in normal functioning or experiences. These symptoms may include:
Schizophrenia can also affect cognitive functioning, leading to problems with attention, memory, and executive functions (such as planning and decision-making). These cognitive impairments can significantly impact daily functioning and overall quality of life.
The symptoms of schizophrenia are chronic and can last for at least six months. The severity and duration of symptoms may vary over time, with periods of exacerbation and remission. The condition can significantly impact the patient’s relationships, education, employment, and overall functioning.
Physical Examination
Schizophrenia is primarily a mental disorder, and its diagnosis is based on the presence of characteristic symptoms rather than physical findings. However, certain physical findings may be observed in individuals with schizophrenia, either as direct consequences of the illness or due to associated factors.
Motor Abnormalities:
Some individuals with schizophrenia may exhibit motor abnormalities, such as:
Motoric immobility: A decrease in spontaneous movement or voluntary actions.
Weight Changes: Schizophrenia can be associated with weight changes due to various factors, including side effects of antipsychotic medications or alterations in appetite and metabolism.
Movement Disorders: In some cases, individuals with schizophrenia may develop movement disorders, such as:
Self-neglect: In severe cases or during periods of active symptoms, individuals with schizophrenia may neglect their personal hygiene, appearance, and self-care, which can lead to physical signs like poor grooming, unkempt hair, and dirty clothing.
Differential Diagnoses
Delusional Disorder
Pervasive developmental disorder
Substance-induced psychotic disorder
Paranoid personality disorder
Schizotypal personality disorder
In the initial treatment of acute psychosis, it is recommended to begin with an oral second-generation antipsychotic medication. Examples of these medications include olanzapine, aripiprazole, risperidone, asenapine, quetiapine, lurasidone, sertindole, brexpiprazole, ziprasidone, molindone, iloperidone, and others.
In some instances, if clinically necessary, a benzodiazepine such as clonazepam, diazepam, or lorazepam may be prescribed alongside the antipsychotic to manage behavioral disturbances and non-acute anxiety.
While first-generation antipsychotics (FGA) like flupentixol, trifluoperazine, fluphenazine, pimozide, haloperidol, sulpiride, chlorpromazine, and others are not commonly used as first-line treatment, they can still be utilized if needed.
Cognitive behavioral therapy (CBT) and art and drama therapies can be beneficial in addressing the disease’s negative symptoms, improving insight, and preventing relapse. These approaches aim to counteract the negative impact of the disease and assist in the patient’s rehabilitation process.
Clozapine is reserved for cases of treatment resistance, with a poor response to at least two different antipsychotic medications. It requires close monitoring, including weekly blood tests for the first six months, biweekly tests for the following six months, and monthly tests to monitor the white blood cell count due to the risk of agranulocytosis.
During the maintenance phase of treatment, prophylaxis and rehabilitation efforts play a vital role in reintegrating patients into the community. It is important to establish the minimum effective dose of antipsychotics during this period.
Substance abuse is common among patients with schizophrenia and can worsen both positive and negative symptoms. Therefore, psychosocial and pharmacotherapeutic approaches should be employed to address substance misuse. In cases of extensive and persistent substance misuse, clozapine may be considered.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914490/
https://www.ncbi.nlm.nih.gov/books/NBK539864/
Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
USA – BOSTON
60 Roberts Drive, Suite 313
North Adams, MA 01247
INDIA – PUNE
7, Shree Krishna, 2nd Floor, Opp Kiosk Koffee, Shirole Lane, Off FC Road, Pune 411004, Maharashtra
Founded in 2014, medtigo is committed to providing high-quality, friendly physicians, transparent pricing, and a focus on building relationships and a lifestyle brand for medical professionals nationwide.
MASSACHUSETTS – USA
60 Roberts Drive, Suite 313,
North Adams, MA 01247
MAHARASHTRA – INDIA
7, Shree Krishna, 2nd Floor,
Opp Kiosk Koffee,
Shirole Lane, Off FC Road,
Pune 411004, Maharashtra
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
On course completion, you will receive a full-sized presentation quality digital certificate.
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
