- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The use of antipsychotic medications, also known as neuroleptic medication or major tranquilizers, is the mainstay of treatment for schizophrenia. These medications have repeatedly been shown to diminish the positive symptoms of schizophrenia and prevent relapses. Approximately 80% of patients relapse within 1 year if antipsychotic medications are stopped, while only 20% relapse if treated. Novel antipsychotic medications are associated with fewer extrapyramidal adverse effects and may be less likely to exacerbate negative and cognitive symptoms of schizophrenia compared to the conventional antipsychotic agents.
The following adverse effects are those typically associated with conventional antipsychotic agents or with risperidone at doses greater than 6 mg/d.
- Akathisia is a subjective sense of inner restlessness, mental unease, irritability, and dysphoria.
- Dystonia is the occurrence of painful and frightening muscle cramps that usually occur within 12-48 hours of the beginning of treatment or an increase in dose. This typically occurs in young muscular men. It affects the head and neck, but it may extend to the trunk and limbs.
- Hyperprolactinemia is associated with galactorrhea, amenorrhea, gynecomastia, impotence, and osteoporosis.
- Neuroleptic malignant syndrome presents with hyperthermia, muscular rigidity, altered mental state, and autonomic instability. Laboratory findings include increased creatine kinase and myoglobinuria. Acute renal failure may be present. A significant mortality rate exists. Rarely, neuroleptic malignant syndrome associated with clozapine and other atypical antipsychotic agents has been reported.
- Parkinsonism presents with tremor, bradykinesia, akinesia, and, sometimes, rigidity or bradyphrenia (slowed thinking). This occurs particularly in women and elderly patients.
- Tardive dyskinesia
- The incidence of tardive dyskinesia (TD) is as high as 70% in elderly patients. It presents as involuntary and repetitive (but not rhythmic) movements of the mouth and face. Chewing, sucking, grimacing, or pouting movements of the facial muscles may occur. People may rock back and forth or tap their feet. Occasionally, diaphragmatic dyskinesia exists, which leads to loud and irregular gasping and/or "jerky" speech. The patient is often not aware of these movements.
- Risk factors for TD include age, female sex, and negative symptoms. Duration of therapy and dose seem to be logical risk factors, but this has not been demonstrated conclusively.
- TD is probably less common with the use of novel antipsychotic drugs but, until many patients have been exposed to these drugs for several years, this will not be known with certainty.
The following adverse effects may occur with all antipsychotic agents, except as noted.
- Anticholinergic side effects include dry mouth, exacerbation of glaucoma, confusion, decreased memory, agitation, visual hallucinations, and constipation. Risperidone, aripiprazole, and ziprasidone are relatively free of anticholinergic adverse effects.
- The QT interval is the electrocardiogram interval between the beginning of the QRS complex and the end of the T wave. It reflects the time required for the ventricles to depolarize and repolarize. When the QT interval is corrected for heart rate, it is called QTc. A prolonged QTc interval puts a person at risk for torsade de pointes, a malignant arrhythmia associated with syncope and sudden death. QTc intervals are lengthened by the conventional antipsychotic agents thioridazine, pimozide, and mesoridazine and, to a lesser extent, by the novel antipsychotic agent ziprasidone. Risk is increased by individual susceptibility, heart failure, bradycardias, electrolyte imbalance (especially hypokalemia), hypomagnesemia, and female gender.19
- As of 2003, no novel antipsychotic agents had been reported to lead to torsade de pointes.
- Haloperidol has only a small influence on the ECG but it has been implicated, although very rarely, in causing torsades de pointes.20
- All antipsychotic agents may be associated with esophageal dysmotility, aspiration, and the subsequent risk of pneumonia.
- Orthostatic hypotension can be problematic at the beginning of therapy, with dose increases, and in elderly patients. This is related to alpha1-blockade and is particularly severe with risperidone and clozapine.
- Venous thromboembolism may be associated with the use of antipsychotic drugs. Patients treated with clozapine may be at particular risk for this complication. The reasons for this possible association are not understood.21,22
- Altered glucose and lipid metabolism, with or without weight gain, may occur with most antipsychotic agents, as can weight gain itself.23 Aripiprazole and ziprasidone are the antipsychotic drugs least likely, and olanzapine and clozapine the most likely, to lead to these adverse effects. The mechanism of weight gain associated with psychotropic drugs is not understood. Sensitivity to insulin may be increased, or increased leptin levels may be present. Weight gain is associated both with psychological problems (eg, decreased self-esteem) and with medical problems (eg, diabetes, coronary artery disease, arthritis). Some approaches to the problem of weight gain include educational programs on nutrition and exercise, and cognitive behavioral therapy. Various medications have been tried but with little success.
The conventional antipsychotic agents are available in generic forms and are less expensive than the newer agents. They are available in a variety of vehicles, including liquid and intramuscular preparations. Most importantly, they are also available as depot preparations. In other countries, several different antipsychotic depot preparations exist, but, in the United States, only haloperidol and fluphenazine are available in depot forms. With respect to the newer agents, risperidone is now available as a long-acting injection (Risperdal Consta) that uses biodegradable polymers.
- Patients may not always take their medications; checking the level can be a clue to this.
- Patients often have other medical illnesses; medicines used in these illnesses can interact with psychotropic medications.
- Patients may not always be the best reporters of their symptoms, and medication levels can occasionally detect clinically silent toxicity.
- Smoking tobacco products induces the liver enzyme CYP1A2, which metabolizes clozapine. Patients who stop smoking while being treated with clozapine often experience an increase in their clozapine levels. (Nicotine patches and nicotine inhalers and chewing tobacco do not induce this enzyme.)
However, many medications do not have clear dose-response curves established. Plasma concentrations of haloperidol are somewhat correlated with clinical effects. Levels of about 15-25 ng/mL are thought to be optimal. Plasma concentrations of clozapine of around 300-400 ng/mL may be optimal.
- Anticholinergic agents (eg, benztropine, procyclidine, trihexyphenidyl, diphenhydramine) or amantadine are often used in conjunction with the conventional antipsychotic agents to prevent dystonic movements or to treat extrapyramidal symptoms. Akathisia is particularly difficult to treat, but it occasionally responds to an anticholinergic agent, a benzodiazepine, or a beta-blocker.
- Clozapine is the oldest atypical antipsychotic agent and probably the most effective.24 It is associated with about a 1% risk of agranulocytosis, so patients must have weekly white blood cell count monitoring for the first 6 months25 (the period of greatest risk) and then monitoring every 2 weeks for 6 months, and then every 4 weeks, as long as the absolute neutrophil count (ANC) is normal. (If the ANC drops, then a strict protocol of monitoring and possibly medication cessation must be followed). Clozapine is also associated with anticholinergic adverse effects, sedation, and drooling.25 Constipation and cardiac side effects (cardiomyopathy and myocarditis) can be life threatening. However, approximately one third of patients who have not responded to conventional antipsychotic agents do better on clozapine. Violence, substance abuse, smoking, and suicidality are diminished with the use of clozapine.
Many patients with schizophrenia are treated with other psychotropic medications in addition to antipsychotic agents. Very little rigorous evidence for the use of polypharmacy in schizophrenia exists, but it is widely practiced. Medications often used include the antidepressants, mood stabilizers, and anxiolytic agents. Note that carbamazepine and clozapine should not be used together. Using 2 or even 3 different antipsychotic agents together is common, although no research supports this (and it is difficult to imagine how such research could be done).
Psychological interventions
Psychosocial treatment for the person with schizophrenia is essential, since medications alone are insufficient. Psychosocial treatments are currently oriented according to the recovery model, which proposes that the successfully treated person with schizophrenia has few or stable symptoms, is not hospitalized, manages his or her own funds and medications, and is either in work or school at least half-time. Hope, empowerment, choice, and community integration are emphasized in this treatment approach.
The best studied psychosocial treatments are social skills training, cognitive behavioral therapy, cognitive remediation, and social cognition training.26
Consultations
Social work: Schizophrenia affects the person's whole family. The effects of familial "high expressed emotion" (hostile overinvolvement and intrusiveness) on the outcome of persons with schizophrenia who return home have generated interest. Some studies have found that family therapy or family interventions may prevent relapse, but these findings have not always been replicated.
Vocational rehabilitation: Few patients with schizophrenia are able to maintain competitive employment. Supported employment programs are associated with higher rates of employment but not with increases in global functioning, self-esteem, time out of the hospital, or quality of life.
Diet
Many psychotropic medications are associated with weight gain and changes in glucose or lipid metabolism. Occasionally the person with schizophrenia develops odd food preferences. Many persons with schizophrenia have limited funds, do not cook for themselves, and live in areas where fast food outlets are abundant. Therefore, nutritional counseling is difficult but important.
Activity
Because many psychotropic medications are associated with weight gain, persons with schizophrenia should be encouraged to be as physically active as possible.
- Most patients with schizophrenia smoke. This may be a result of previous conventional antipsychotic treatment because nicotine may ameliorate some of the adverse effects of these drugs. Smoking may also be related to the boredom associated with hospitalizations, the peer pressure from other patients to smoke, or the anomie associated with unemployment. The health risks from smoking are well known, and patients should be encouraged to stop smoking. Cessation of tobacco smoking, however, may result in the unexpected increase of clozapine levels.
- Involving people outside the usual medical settings is also helpful. The National Alliance for the Mentally Ill (NAMI) is a helpful advocacy group that is supportive for family members. NAMI also advocates funding and research. Patients with schizophrenia often have difficulty finding housing; therefore, working with associations that may provide housing assistance is important.
Medication
The medications listed below diminish the positive symptoms of schizophrenia and prevent relapses. The newer, or atypical, antipsychotic drugs may be more effective in treating negative symptoms and cognitive impairment.All medications should be used in lower doses with children and elderly patients and with great caution in women who are pregnant or breastfeeding.
Antipsychotics
Mainstay of treatment of schizophrenia. Some clinicians routinely perform ECGs on patients before beginning treatment with antipsychotic medication. Note that the use of antipsychotic medications for the treatment of behavioral symptoms in elderly patients with dementia has not been shown to be effective and is associated with an increased risk of mortality. Because suicide is not uncommon in patients with psychotic illnesses, the clinicians should write prescriptions for the smallest quantity that is consistent with good clinical care. Patients should be urged to avoid substance abuse.
Aripiprazole (Abilify)
A partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. Also antagonizes alpha1 receptors. Available as tab, orally disintegrating tab, or oral solution.
Adult
10-15 mg PO qd; if needed, may increase dose gradually q2wk, not to exceed 30 mg/d
Alternatively, 9.75 mg IM initially (dose range 5.25 to 15 mg); may give second dose after minimum of 2 h; not to exceed total cumulative dose of 30 mg/d; replace injection with oral dose (10-30 mg/d) as soon as possible
Pediatric
Not established
CYP450 3A4 and 2D6 isoenzyme substrate, thus, inhibitors (ie, ketoconazole, quinidine, fluoxetine, paroxetine) or inducers (ie, carbamazepine) may increase or decrease serum levels respectively
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include headache, anxiety, somnolence, or insomnia; rare reports of tardive dyskinesia and neuroleptic malignant syndrome; may cause orthostatic hypotension, seizure, dysphagia, or suicidal ideation; hyperglycemia may occur and in some cases be extreme, resulting in ketoacidosis, hyperosmolar coma, or death
Clozapine (Clozaril)
Antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors. Has some D2 antagonism and high D4 affinity.
Adult
25 mg PO qd or bid initial, gradually increase to a therapeutic target dose of 300-450 mg/d; maximum dose is 900 mg/d
Pediatric
Not established
Epinephrine and phenytoin may decrease effects; tricyclic antidepressants, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects; do not administer with carbamazepine or any drugs known to suppress bone marrow function; benzodiazepines should be used with clozapine with caution because of some cases of cardiopulmonary collapse
Documented hypersensitivity; paralytic ileus; WBC count <3500 cells/mm3 or absolute neutrophil count (ANC) < 2000/mm before or during therapy; history of myeloproliferative disorder or uncontrolled seizure disorder
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not stop the medication abruptly; perform ANC count testing qwk for the first 6 mo, then q2wk for 6 months, then q4wk for the duration; monitor for treatment-emergent adverse effects such as hypotension, myoclonic jerks and seizures, urinary incontinence or retention, and constipation; there are clearly outlined parameters for blood monitoring which must be followed; some clinicians follow electrocardiograms, temperature, and vital signs closely in first few weeks of treatment because of possibility of myocarditis or cardiomyopathy
Fluphenazine hydrochloride (Prolixin)
High-potency typical antipsychotic that blocks postsynaptic dopaminergic D1 and D2 receptors in the brain. Some alpha-adrenergic and anticholinergic effects and may depress the reticular activating system.
Adult
2.5-10 mg/d PO; may increase to maximum 40 mg/d
Decanoate: 50 mg IM q1-4wk as needed and tolerated; may treat some patients with higher doses
Pediatric
Safety and efficacy in children has not been established.
0.25-0.75 mg PO qd/qid
Decanoate form:
<5 years: Not established
5-12 years: 3.125-12.5 mg IM q1-3wk as needed and tolerated
>12 years: 12.5-25 mg IM q1-3wk as needed and tolerated
May potentiate effects of narcotics including respiratory depression; CNS effects increase when coadministered with lithium; barbiturates may decrease effects of fluphenazine
Documented hypersensitivity; narrow-angle glaucoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause hypotension, orthostatic hypotension, photosensitivity, constipation, xerostomia, akathisia, dizziness, tardive dystonia, Parkinsonism, tardive dyskinesia, blurred vision; use the abnormal involuntary movement scale (AIMS) to check for development of tardive dyskinesia
Mild leukocytosis, leukopenia, and eosinophilia occasionally occur; dermatologic reactions are common; watch for urinary retention, blurred vision, dry mouth, and constipation as a result of anticholinergic effects
Haloperidol (Haldol)
Drug of choice for patients with acute psychosis when no contraindications exist. Haloperidol is a D2 antagonist. Butyrophenone noted for high potency and low potential for causing orthostasis. The drawback is the high potential for EPS/dystonia. Parenteral dosage form may be admixed in same syringe with 2 mg of lorazepam for better anxiolytic effects.
Adult
0.5-5 mg PO bid/tid (up to 30 mg/d)
2-5 mg IM q4-8h prn
Decanoate form: If person is stabilized on a dose of oral haloperidol up to 10 mg/d, use 10 to 15 times the daily oral dose IM q4wk; if person is stabilized on a higher dose of oral haloperidol, use 20 times oral dose IM for first 4 wk; then 10-15 times previous daily oral dose q4wk; initial doses should not exceed 100 mg
Pediatric
<3 years: Not established
3-12 years:
Initial: 0.05 mg/kg/d PO or 0.25-0.5 mg/d PO bid/tid, increase by 0.25-0.5 mg q5-7d
Maintenance: not to exceed 0.15 mg/kg/d, give in divided doses
>12 years: Administer as in adults
May increase tricyclic antidepressant serum concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects of haloperidol; haloperidol coadministration with anticholinergics may increase intraocular pressure; encephalopathic syndrome associated with concurrent administration of lithium and haloperidol
Documented hypersensitivity; narrow-angle glaucoma; bone marrow suppression; severe cardiac or liver disease; severe hypotension; subcortical brain damage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
If used as a maintenance medication, use the abnormal involuntary movement scale (AIMS) to check for the development of tardive dyskinesia; if IV/IM, monitor for hypotension; caution in diagnosed CNS depression or cardiac disease; in history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if occurs)
Olanzapine (Zyprexa)
Olanzapine is a selective monoaminergic antagonist at the following receptors: serotonin, D1-4, muscarinic, H1, and alpha1 adrenergic.
Adult
5-10 mg PO qd, increase to 10 mg PO qd within 5-7 d, adjust by 5 mg/d at 1-wk intervals to a recommended maximum of 20 mg/d; many clinicians use higher doses
Pediatric
<13 years: Not established
Adolescents (13-17 years): 2.5-5 mg PO qd initially; target dose is 10 mg/day; adjust by dose increments/decrements of 2.5-5 mg
Dosage range: 2.5-20 mg/day
Weight gain and hyperlipidemia: Consider increased potential (in adolescents as compared with adults) for weight gain and hyperlipidemia; clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents
Fluvoxamine may increase effects of olanzapine; antihypertensives may increase risk of hypotension and orthostatic hypotension; levodopa, pergolide, bromocriptine, charcoal, carbamazepine, omeprazole, rifampin, and cigarette smoking may decrease the effects of olanzapine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in narrow-angle glaucoma, cardiovascular disease, cerebrovascular disease, prostatic hypertrophy, seizure disorders, hypovolemia, and dehydration; may lead to weight gain and disturbances in glucose and lipid regulation; a small risk of seizures may exist
Paliperidone (Invega)
Major active metabolite of risperidone and first oral agent allowing once-daily dosing. Indicated for treatment of acute schizophrenia. Mechanism of action not completely understood but thought to mediate central receptor antagonism of dopamine type 2 (D2) and serotonin type 2 (5HT2A). Also elicits antagonist activity at adrenergic alpha1 and alpha2 receptors and histamine-1 receptors. Has no affinity for cholinergic, muscarinic, or beta-adrenergic receptors. Available as extended-release drug delivery system via osmotic pressure.
Adult
6 mg PO qd initially; if needed, may increase by 3-mg increments after at least 5 d; not to exceed 12 mg/d; some patients respond to lower doses of 3 mg/d
CrCl >50 to <80 mL/min: Not to exceed daily dose of 6 mg
CrCl 10 to <50 mL/min: Not to exceed daily dose of 3 mg
Pediatric
<18 years: Not established
Not substantially metabolized by cytochrome P450 isoenzymes and does not inhibit P-glycoprotein; may increase arrhythmia risk when coadministered with other drugs known to prolong QTc (eg, class IA [quinidine, procainamide] or class III [amiodarone, sotalol] antiarrhythmics, antipsychotics [chlorpromazine, thioridazine], antibiotics [gatifloxacin, moxifloxacin]); coadministration with other CNS depressants, including alcohol, may cause additive effects; coadministration with other drugs causing orthostatic hypotension (eg, alpha-blockers, diuretics) may increase hypotension risk; may antagonize effect of dopamine agonists (eg, levodopa, pramipexole)
Documented hypersensitivity to paliperidone or risperidone
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Decrease dose in renal impairment; causes modest QTc prolongation; other adverse effects include tachycardia, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia (some with associated ketoacidosis, hyperosmolar coma, or death), orthostatic hypotension and syncope, hyperprolactinemia, sedation, priapism, thrombotic thrombocytopenia purpura, disrupted body temperature regulation, and antiemetic effector dysphagia
Avoid with preexisting gastrointestinal narrowing (eg, esophageal motility disorders, small bowel inflammatory disease, short gut syndrome, peritonitis, cystic fibrosis, chronic pseudoobstruction, Meckel diverticulum) because tab is nondeformable and does not appreciably change in shape or size through gut and is eliminated intact in feces; swallow tab whole (do not chew or split)
Risperidone (Risperdal)
Has both D2 and serotonin 5HT2 antagonism. Now available in long-acting form using microspheres made of biodegradable polymers.
Adult
1 mg PO bid initial, slowly increase to optimum range of 4-8 mg/d; doses >10 mg/d do not appear to offer additional benefit; use lower doses in elderly patients
If using long-acting risperidone (Risperdal Consta), dose can be started at 25 mg IM q2wk, this needs to be supplemented with PO risperidone for first 3 wk
Pediatric
Not established
Coadministration with carbamazepine may decrease effects; risperidone may inhibit effects of levodopa; clozapine may increase risperidone levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause extrapyramidal reactions, hyperprolactinemia, hypotension, tachycardia, and arrhythmias
Quetiapine (Seroquel)
May act by antagonizing dopamine and serotonin effects. Newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.
Adult
Initial: 25 mg PO bid/tid; increase by 25-50 mg bid/tid on day 2 or 3 to achieve range of 300-400 mg divided bid/tid by day 4; adjust as needed at intervals of at least 2 d with adjustments of 25-50 mg bid
Maintenance: 150-750 mg/d PO; not to exceed 800 mg/d, though some clinicians use higher doses
Pediatric
Not established
May antagonize levodopa and dopamine agonists; phenytoin, thioridazine, and other liver enzyme inducers may reduce quetiapine levels; CYP450 3A inhibitors (eg, ketoconazole, fluconazole, erythromycin) increase quetiapine serum concentration
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; the neuroleptic malignant syndrome and tardive dyskinesia have been associated with this treatment
Ziprasidone (Geodon)
Antipsychotic agent that antagonizes dopamine type-2, 5-HT2, histamine H1, and alpha1-adrenergic receptors.
Adult
20 mg PO bid initial; may increase gradually (q2-3d); not to exceed 160 mg/d, though some clinicians use higher doses
Pediatric
Not established
CYP450-3A4 inhibitors (eg, erythromycin, ketoconazole) may increase serum levels; CYP450-3A4 inducers (eg, carbamazepine, rifampin) may decrease serum levels; coadministration with drugs that increase QT/QTc interval (eg, amiodarone, fluoroquinolones) increases risk of life-threatening arrhythmias
Documented hypersensitivity; QTc prolongation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolongs QT/QTc (caution in patients with known risk factors, eg, hypomagnesemia, hypokalemia); caution in seizure disorders; may cause hypotension, extrapyramidal symptoms, and somnolence
Iloperidone (Fanapt)
Atypical antipsychotic agent indicated for acute treatment of schizophrenia. Precise mechanism of action unknown. Antagonizes receptors for dopamine-2 and serotonin type 2 (5-HT2). Approved by FDA in May 2009.
Adult
1 mg PO bid initially on day 1; to reach target dose of 12-24 mg/d, adjust dose daily by smallest possible increments (ie, 2 mg bid on day 2; 4 mg bid on day 3; 6 mg bid on day 4) to avoid orthostatic hypotension
Pediatric
<18 years: Not established
CYP3A4 and CYP2D6 substrate; CYP3A4 inhibitors (eg, ketoconazole) or CYP2D6 inhibitors (eg, fluoxetine, paroxetine) may inhibit elimination and increase blood levels; do not use with other drugs that prolong QT interval (eg, class 1A antiarrhythmics [quinidine, procainamide], class III antiarrhythmics [amiodarone, sotalol], antipsychotics [chlorpromazine, thioridazine], antibiotics [moxifloxacin, erythromycin]); additive CNS effects may occur when coadministered with other centrally acting drugs or alcohol
Documented hypersensitivity; coadministration with other drugs that prolong QT interval
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common dose-related adverse effects include dizziness, xerostomia, fatigue, nasal congestion, orthostatic hypotension and syncope, tachycardia, and weight gain; serious adverse effects include QT interval prolongation, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, seizures, leukopenia, neutropenia, agranulocytosis, hyperprolactinemia, disruption of body temperature, and dysphagia; avoid with hepatic impairment
Asenapine (Saphris)
Mechanism of action unknown. Efficacy thought to be mediated through a combination of antagonist activity at dopamine 2 and serotonin (5-HT2) receptors. Exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors; dopamine D2, D3, D4, and D1 receptors; alpha1- and alpha2-adrenergic receptors; and histamine H1 receptors, with moderate affinity for H2 receptors. In vitro assays suggest antagonistic activity elicited at these receptors. Indicated for acute treatment of schizophrenia.
Adult
5 mg SL bid; if patient responds favorably, continue beyond initial acute phase (currently no recommendations for duration of therapy)
Pediatric
Not established
Metabolized via UGT1A4 and CYP450 (predominantly isoenzyme 1A2); weak inhibitor of CYP2D6; coadministration with other drugs that prolong QTc interval may result in life-threatening arrhythmias (eg, class 1A antiarrhythmics [quinidine, procainamide], class 3 antiarrhythmics [amiodarone, sotalol], antipsychotics [ziprasidone, chlorpromazine, thioridazine], and antibiotics [gatifloxacin, moxifloxacin]); concurrent use of CNS-acting drugs or alcohol may increase toxicity
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects while treating schizophrenia include akathisia, oral hypoesthesia, and dizziness; common adverse effects while treating bipolar disorder include drowsiness, dizziness, and movement disorders other than akathisia; may cause neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control), and weight gain; may cause hypotension and syncope, especially early in treatment because of its alpha1-antagonistic activity; may cause leukopenia, neutropenia, and agranulocytosis; may prolong QTc interval (avoid with history of cardiac arrhythmias and other conditions that increase risk for Torsade de Pointes [eg, bradycardia, hypokalemia, hypomagnesemia]); may increase risk of hyperprolactinemia, seizures, cognitive/motor impairment, and dysphagia; may disrupt body temperature regulation; not recommended with severe hepatic impairment (ie, Child-Pugh C); inherent suicide risk with population treated warrants close supervision when changing drug therapy
Boxed warning: Use of antipsychotic drugs to treat elderly patients with dementia-related psychosis has been found to increase risk of death (not approved for dementia-related psychosis)
More on Schizophrenia |
| Overview: Schizophrenia |
| Differential Diagnoses & Workup: Schizophrenia |
 Treatment & Medication: Schizophrenia |
| Follow-up: Schizophrenia |
| References |
| Further Reading |
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Keywords
schizophrenia, schizophrenia symptoms, schizophrenia test, childhood schizophrenia, schizophrenic, signs of schizophrenia, dementia praecox, auditory hallucinations, impaired information processing, delusions, disorganized speech, disorganized behavior, psychiatric disorders, thought disturbances, distorted thinking, mental illness, psychosis, mental disorder, delusions, depression, mania, manic depressive, major depressive disorder, mood disorder, bipolar disorder
