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Special Alerts
Antipsychotics: Newborn Extrapyramidal and Withdrawal Symptoms with Third Trimester Exposure (Update)
June 2011
The U.S. Food and Drug Administration (FDA) and Health Canada have updated or are in the process of updating the pregnancy sections of their respective prescribing information for antipsychotics to contain detailed information about nonteratogenic effects following maternal use during pregnancy. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms; EPS) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects vary in severity and may be self-limiting (subsiding within hours or days) or require hospitalization. In the cases reported to the FDA, concomitant use of other medications (known to precipitate withdrawal symptoms) may have contributed to the effects, although in some cases, antipsychotic medication use was the only contributing factor for the EPS and withdrawal symptoms.
Women who are taking antipsychotics should not stop them if they become pregnant (abrupt discontinuation is not recommended), but should notify their healthcare provider. Women taking antipsychotics who intend to become pregnant should discuss treatment concerns with their healthcare provider. Any adverse effects noted in newborns should be reported in the U.S. to the FDA's Medwatch program (1-800-332-1088 or https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm) or in Canada to Health Canada's Canada Vigilance Program (1-866-234-2345 or http://www.hc-sc.gc.ca/dhp-mps/medeff/index-eng.php).
For additional information, please refer to:
U.S.: http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm#aihp
Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2011/2011_78-eng.php
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(per FEN a zeen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of schizophrenia; severe nausea and vomiting
Use: Unlabeled
Psychosis; psychosis/agitation related to Alzheimer's dementia (risks vs benefits)
Pregnancy Considerations
Jaundice or hyper/hyporeflexia have been reported in newborn infants following maternal use of phenothiazines. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.
Breast-Feeding Considerations
Based on information from two mother-infant pairs, following maternal use of perphenazine 16-24 mg/day, the estimated exposure to the breast-feeding infant would be 0.1% to 0.2% of the weight-adjusted maternal dose. Adverse events have not been reported in nursing infants (information from four cases). Infants should be monitored for signs of adverse events; routine monitoring of infant serum concentrations is not recommended.
Contraindications
Hypersensitivity to perphenazine or any component of the formulation (cross-reactivity between phenothiazines may occur); severe CNS depression (comatose or patients receiving large doses of CNS depressants); subcortical brain damage (with or without hypothalamic damage); bone marrow suppression; blood dyscrasias; liver damage
Warnings/Precautions
Boxed warnings:
• Dementia: See “Disease-related concerns” below.
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, perphenazine has a low potency of cholinergic blockade.
• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, pre-existing low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1000/mm3.
• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (eg, Alzheimer's disease).
• Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Risk of tardive dyskinesia and potential for irreversibility often associated with total cumulative dose and therapy duration and may also be increased in elderly patients (particularly elderly women); antipsychotics may also mask signs/symptoms of tardive dyskinesia.
• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• Neuroleptic malignant syndrome (NMS): May be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability.
• Ocular effects: May cause pigmentary retinopathy, and lenticular and corneal deposits, particularly with prolonged therapy.
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Photosensitivity: May cause photosensitization; avoid prolonged exposure to sunlight.
• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.
• Dementia: [U.S. Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Perphenazine is not approved for the treatment of dementia-related psychosis.
• Depression: Use with caution in patients with depression; possibility of increased risk of suicide; limit quantities of drug available until significant remission observed.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.
• Hepatic impairment: Monitor hepatic function during use; discontinue if abnormalities occur; contraindicated in patients with liver damage.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; condition may be exacerbated by cholinergic blockade.
• Parkinson's disease: Use with caution in patients with Parkinson's disease; they may be more sensitive to adverse effects.
• Renal impairment: Use with caution in patients with renal impairment. Monitor renal function during therapy; discontinue if BUN abnormalities occur.
• Respiratory disease: Use with caution in patients with respiratory disease.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
Concurrent drug therapy issues:
• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye's syndrome, brain tumor) due to antiemetic effects.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use with caution in the elderly; potential for an increased risk of adverse events (eg, sedation, orthostatic hypotension, anticholinergic effects) and an increased risk for developing tardive dyskinesia, particularly in elderly women.
• Poor metabolizers: Use with caution in patients with reduced functional alleles of CYP2D6. Poor metabolizers may have higher plasma concentrations at usual doses, increasing risk for adverse reactions.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, cardiac arrest, ECG changes, hyper-/hypotension, orthostatic hypotension, pallor, peripheral edema, sudden death, tachycardia
Central nervous system: Bizarre dreams, catatonic-like states, cerebral edema, dizziness, drowsiness, extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia), faintness, headache, hyperactivity, hyperpyrexia, impairment of temperature regulation, insomnia, lethargy, neuroleptic malignant syndrome (NMS), nocturnal confusion, paradoxical excitement, paranoid reactions, restlessness, seizure
Dermatologic: Discoloration of skin (blue-gray), photosensitivity
Endocrine & metabolic: Amenorrhea, breast enlargement, hyper-/hypoglycemia, galactorrhea, lactation, libido changes, gynecomastia, menstrual irregularity, parotid swelling (rare), SIADH
Gastrointestinal: Adynamic ileus, anorexia, appetite increased, constipation, diarrhea, fecal impaction, obstipation, nausea, salivation, vomiting, weight gain, xerostomia
Genitourinary: Bladder paralysis, ejaculatory disturbances, incontinence, polyuria, urinary retention
Hematologic: Agranulocytosis, eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenic purpura
Hepatic: Hepatotoxicity, jaundice
Neuromuscular & skeletal: Muscle weakness
Ocular: Blurred vision, cornea and lens changes, epithelial keratopathies, glaucoma, mydriasis, myosis, photophobia, pigmentary retinopathy
Renal: Glycosuria
Respiratory: Nasal congestion
Miscellaneous: Allergic reactions, diaphoresis, systemic lupus erythematosus-like syndrome
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP2D6 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotics. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: Antipsychotics may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Analgesics (Opioid): Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Antacids: May decrease the absorption of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Antimalarial Agents: May increase the serum concentration of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy
Anti-Parkinson's Agents (Dopamine Agonist): May diminish the therapeutic effect of Antipsychotics (Typical). Antipsychotics (Typical) may enhance the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson's agents. Risk D: Consider therapy modification
Beta-Blockers: Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lithium formulations: May enhance the neurotoxic effect of Antipsychotics. Lithium formulations may decrease the serum concentration of Antipsychotics. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Methylphenidate: Antipsychotics may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotics. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Quinagolide: Antipsychotics may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotics. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid kava kava, gotu kola, valerian, St John's wort (may increase CNS depression).
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.
Mechanism of Action
Perphenazine is a piperazine phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones
Pharmacodynamics/Kinetics
Absorption: Oral: Well absorbed
Metabolism: Extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine)
Half-life elimination: Perphenazine: 9-12 hours; 7-hydroxyperphenazine: 10-19 hours
Time to peak, serum: Perphenazine: 1-3 hours; 7-hydroxyperphenazine: 2-4 hours
Excretion: Urine and feces
Dosage
Oral:
Adults:
Schizophrenia:
Nonhospitalized: Initial: 4-8 mg 3 times/day; reduce dose as soon as possible to minimum effective dosage (maximum: 24 mg/day)
Hospitalized: 8-16 mg 2-4 times/day (maximum: 64 mg/day)
Nausea/vomiting: 8-16 mg/day in divided doses; reduce dose as soon as possible to minimum effective dosage (maximum: 24 mg/day)
Elderly: No dosage adjustment provided in manufacturer's labeling; however, initiate dosing at the lower end of the dosing range. Refer to adult dosing.
Dosing adjustment in renal impairment: 0% to 5% removed by hemodialysis (HD); no dosage adjustment provided in manufacturer's labeling.
Dosing adjustment in hepatic impairment: No dosage adjustment provided in manufacturer's labeling.
Administration: Oral
May be administered without regard to meals.
Monitoring Parameters
Vital signs; lipid profile, fasting blood glucose/Hgb A1c, liver and kidney function (periodically during therapy), CBC (prior to and periodically during therapy); BMI; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS)
Reference Range
2-6 nmol/L
Patient Education
It may take 2-3 weeks to achieve desired results. Avoid alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience excess drowsiness, restlessness, dizziness, blurred vision, dry mouth, nausea, vomiting, constipation, postural hypotension, urinary retention, photosensitivity, or decreased perspiration. Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, confusion); chest pain, palpitations, or rapid heartbeat; severe dizziness; unresolved urinary retention; change in libido or ejaculatory difficulty; vision changes; skin rash or yellowing of skin; respiratory difficulty; or worsening of condition.
Geriatric Considerations
Any changes in disease status in any organ system can result in behavior changes.
Many elderly patients receive antipsychotic medications for inappropriate nonpsychotic behavior. Before initiating antipsychotic medication, the clinician should investigate any possible reversible cause; any stress or stress from any disease can cause acute “confusion” or worsening of baseline nonpsychotic behavior. Most commonly acute changes in behavior are due to increases in drug dose or addition of new drug to regimen; fluid electrolyte loss; infections; and changes in environment.
In the treatment of agitated, demented, elderly patients, authors of meta-analysis of controlled trials of the response to the traditional antipsychotics (phenothiazines, butyrophenones) in controlling agitation have concluded that the use of neuroleptics results in a response rate of 18%. Clearly neuroleptic therapy for behavior control should be limited with frequent attempts to withdraw the agent given for behavior control.
Anesthesia and Critical Care Concerns/Other Considerations
Coadministration of two or more antipsychotics does not improve clinical response and may increase the potential for adverse effects.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment:
Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension.
Tardive dyskinesia: Prevalence rate may be 40% in elderly; development of the syndrome and the irreversible nature are proportional to duration and total cumulative dose over time. Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age. Drug-induced Parkinson's syndrome occurs often; akathisia is the most common extrapyramidal reaction in elderly.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called “epinephrine reversal” phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.
Mental Health: Comment
Perphenazine is an intermediate-potency antipsychotic. Older antipsychotic medications (chlorpromazine, haloperidol), which do not meet specific criteria for “atypical” antipsychotics, are often referred to as typical antipsychotics. They are associated with the troubling side effect, EPS. However, it is commonly believed that in order for a drug to treat psychosis, it must block dopamine is some manner.
Common side effects include sedation and neuroleptic effect (reduced initiative, interest in the environment, and display of emotion or affect). All typical antipsychotics are considered to be equally effective if given in equipotent doses. An inverse relationship exists between intrinsic antimuscarinic activity and propensity to cause extrapyramidal side effects. If dystonia or pseudoparkinsonism occurs, antiparkinsonian agents should be considered. If akathisia occurs, beta-blockers (eg, propranolol), benzodiazepines, or antiparkinsonian agents should be considered. Tardive dyskinesia (TD) secondary to typical antipsychotics has an estimated incidence of 3% to 5% per year for the first 5 years of treatment. After this time period, the incidence is estimated to be 2% to 3% per year. Prevalence rates are approximately 15% to 20%. Female gender and age constitute risk factors for TD. Indeed, prevalence rates have been reported to be as high as 70% in elderly females. No specific treatment exists for TD, however, patients are often initiated on/switched to an atypical antipsychotic because of their lower incidence to cause TD and hopes of suppression.
Typical antipsychotics are usually only indicated for schizophrenia, but are generally effective for mania and psychosis and/or behavioral syndromes secondary to other mental conditions. Nonpsychiatric uses include Tourette's syndrome, Huntington's disease, and occasionally, intractable hiccups, pruritus, nausea, and vomiting.
These drugs are thought to exert their antipsychotic activity by blocking dopamine D2 receptors in the mesolimbic dopaminergic pathway. Side effects are often related to their ability to antagonize dopamine receptors in the nigrostriatal and tuberoinfundibular pathways.
Coadministration of two or more antipsychotics does not generally improve clinical response and may increase the potential for adverse effects.
In 2008, the FDA issued a warning regarding increased mortality risk with typical and atypical antipsychotic drugs when used in elderly patients with dementia-related psychosis.
Nursing: Physical Assessment/Monitoring
Monitor ophthalmic screening at beginning of therapy and periodically throughout. Monitor blood pressure; can cause orthostatic hypotension. Initiate at lower doses and taper dosage slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 2 mg, 4 mg, 8 mg, 16 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Perphenazine)
2 mg (60): $51.99
4 mg (60): $69.99
8 mg (60): $76.99
16 mg (60): $107.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Azaz-Livshits TL, Symmer LI, and Fraenkel YM, “Atypical Neuroleptic Malignant Syndrome Presenting as Rhabdomyolysis, Altered Consciousness, and Leukocytosis,” J Pharm Technol, 1995, 11:173-5.
Fortinguerra F, Clavenna A, and Bonati M, "Psychotropic Drug Use During Breastfeeding: A Review of the Evidence," Pediatrics, 2009, 124(4):e547-56.
Gill SS, Bronskill SE, Normand SL, et al, “Antipsychotic Drug Use and Mortality in Older Adults With Dementia,” Ann Intern Med, 2007, 146(11):775-86.
Hansen LB and Larsen NE, “Metabolic Interaction Between Perphenazine and Disulfiram,” Lancet, 1982, 2(8313):1472.
Harper G, Dawes M, Azlin C, et al, “Small Bowel Obstruction in a Child on an Antipsychotic,” J Child Adolesc Psychopharmacol, 1995, 5:81-4.
Lieberman JA, Stroup TS, McEvoy JP, et al, “Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizophrenia,” N Engl J Med, 2005, 353(12):1209-23.
Moore TA, “Schizophrenia Treatment Guidelines in the United States,” Clin Schizophr Relat Psychoses, 2011, 5(1):40-9.
National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health , “Schizophrenia. Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care (Updated),” National Clinical Practice Guideline Number 82, 2009:1-399. Available at www.nice.org.uk/cg082
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
Schneeweiss S, Setoguchi S, Brookhart A, et al, “Risk of Death Associated With the Use of Conventional Versus Atypical Antipsychotic Drugs Among Elderly Patients,” CMAJ, 2007, 176(5): 627-32.
Seifert RD, “Therapeutic Drug Monitoring: Psychotropic Drugs,” J Pharm Pract, 1984, 6:403-16.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
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