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.
| 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 |