Supplement: Second-Generation Antipsychotic Drugs

Second-Generation Antipsychotic Drugs This table lists the atypical antipsychotics. For a story on the lessons of the CATIE trial, click here. For a table of first-generation drugs, click here. For a table of drugs in the pipeline, click here. Drug Brand name(Manufacturer) Approval date Indications Mechanism Cost per 30-day supply* Contraindications/Adverse reactions Injection availability Other data Clozapine Clozaril (Novartis) FazaClo (now available as a generic) (Azur Pharma) September 1989 (Clozaril); February 2004 (FazaClo) Treatment-resistant schizophrenia Interferes with binding of dopamine D1, D2, D3 and D5 receptors; affinity for D4, also has affinity for serotonergic receptors $313.85, (600 mg/day) Agranulocytosis, eosinophilia, seizure, myocarditis, weight gain, diabetes mellitus, NMS, TD, IMDRP "Clozapine is different from every other drug out there," says Joseph Coyle of Harvard Medical School. For example, 90% of schizophrenia patients smoke, says Coyle. On Clozapine, 50% of them stop smoking. Clozapine also has the highest frequency and rate of weight gain of all the antipsychotics. Risperidone Risperdal (Janssen) December 1993 Schizophrenia, bipolar mania Antagonist with high affinity for serotonin 5HT2, dopamine D2, a1 and a2 adrenergic, and H1 histaminergic receptors; low to moderate affinity for the serotonin 5HT1C, 5HT1D, and 5HT1A receptors; weak affinity for dopamine D1 $604.08, (8 mg/day) IMDRP, NMS, TD, hyperglycemia and diabetes mellitus, orthostatic hypotension, seizures, dysphagia, hyperprolactinemia, anxiety, somnolence, extrapyramidal symptoms, dizziness, constipation, nausea, dyspepsia, rhinitis, rash, and tachycardia IM One study funded by Bristol-Myers Squibb (J Clin Psychiat, 68 Suppl 7:1-48, 2007) found that experts favored risperidone for the treatment of a healthy young man with schizophrenia of normal weight, lipid levels and fasting glucose and who is having an acute psychotic episode. The study assumes a patient of unknown medical history currently on no medications. Olanzapine Zyprexa (Lilly) September 1996 Schizophrenia, acute mixed or manic episodes with bipolar I dis-order, agitation associated with schizophrenia and bipolar I mania Unknown: likely dopamine and serotonin receptors $553.00, (12.5 mg/day) NMS, TD, postural hypotension, tachycardia, hypertension, hypotension, somnolence, dizziness, asthenia, parkinsonism, insomnia, personality disorder IM Olanzapine is second to clozapine in the magnitude of weight gain among patients, and bears a high risk of diabetes compared to the other antipsychotics. Quetiapine Fumarate Seroquel (AstraZeneca) September 1997 Schizophrenia, bipolar disorder Antagonist at serotonin 5HT1A and 5HT2, dopamine D1 and D2, histamine H1, and adrenergic a1 and a2 receptors $261.61, (300 mg/day) Contraindicated for people with major depressive disorder; IMDRP, suicide, NMS, TD, hyperglycemia and diabetes mellitus, somnolence, headache, dizziness, dry mouth Quetiapine is second to clozapine in minimizing extrapyramidal side effects, according to a Canadian review, The RxFiles, from Saskatoon City Hospital. Ziprasidone Hydrochloride Geodon (Pfizer) February 2001 Schizophrenia, bipolar disorder and agitation associated with schizophrenia or bipolar disorder Affinity for dopamine D2 and D3 and serotonin 5HT2A, 5HT2C, 5HT1A, 5HT1D and a1-adrenergic receptors; moderate affinity for histamine H1 receptor; antagonist at the D2, 5HT2A, and 5HT1D receptors; agonist at the 5HT1A receptor $170.09, (60 mg/day) QT prolongation, hypersensitivity, IMDRP, NMS, TD, hyperglycemia and diabetes mellitus IM Ziprasidone bears the highest risk for prolongation of the QTc interval. Aripiprazole Abilify (Bristol-Myers Squibb and Otsuka America Pharmaceutical) November 2002 Schizophrenia, bipolar disorder and agitation associated with schizophrenia or bipolar disorder Affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A; moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors; moderate affinity for the serotonin reuptake site; agonist at the dopamine D2 and the serotonin 5-HT1A receptors; antagonist at serotonin 5-HT2A receptor $354.05, (15 mg/day) Increased mortality in elderly patients with dementia-related psychosis (IMDRP); neuroleptic malignant syndrome (NMS); tardive dyskinesia (TD); cerebrovascular adverse events; hyperglycemia and diabetes mellitus; orthostatic hypotension; seizure IM Unlike many of the other typical or atypical antipsychotics, aripiprazole isn?t associated with weight gain, note several scientists. Thus it is preferred for overweight or obese patients. Paliperidone Invega (Janssen) December 2006 Schizophrenia Antagonist at D2, serotonin 5HT2A, D1 and D2 adrenergic receptors, and H1 histaminergic receptors $316.76, (6 mg/day) IMDRP, NMS, TD, QT prolongation, hyperglycemia and diabetes mellitus, orthostatic hypotension and syncope, seizure, hyperprolactinemia ARTICLE EXTRAS The Treatments | A Troubled History | The Atypical Atypical? | The next generation? | The Lessons of CATIE | Beyond Drugs | Nonmedication Therapies

Supplement: Second-Generation Antipsychotic Drugs

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Drug	Brand name(Manufacturer)	Approval date	Indications	Mechanism	Cost per 30-day supply*	Contraindications/Adverse reactions	Injection availability	Other data
Clozapine	Clozaril (Novartis) FazaClo (now available as a generic) (Azur Pharma)	September 1989 (Clozaril); February 2004 (FazaClo)	Treatment-resistant schizophrenia	Interferes with binding of dopamine D1, D2, D3 and D5 receptors; affinity for D4, also has affinity for serotonergic receptors	$313.85, (600 mg/day)	Agranulocytosis, eosinophilia, seizure, myocarditis, weight gain, diabetes mellitus, NMS, TD, IMDRP		"Clozapine is different from every other drug out there," says Joseph Coyle of Harvard Medical School. For example, 90% of schizophrenia patients smoke, says Coyle. On Clozapine, 50% of them stop smoking. Clozapine also has the highest frequency...