Choice Of Antipsychotic Drug Research Articles

Antipsychotic use in a large community sample of patients with delusional disorder

BackgroundTo examine clinical and sociodemographic differences between patients with delusional disorder; with and without diagnoses of an additional severe mental disorder (SMD) or cognitive impairment. MethodsPopulation-based study including all individuals diagnosed with DD between 2005 and 2021 from a large catchment area in Madrid, Spain. Sociodemographic and clinical characteristics and the antipsychotic prescription patterns of the study population was described. Patients were divided into (i) patients with DD and no additional diagnosis of SMD or cognitive impairment (DD group), (ii) patients with DD and a diagnosis of an additional SMD (DD-SMD group), and (iii) patients with DD and cognitive impairment (DD-CI group). ResultsOf 1109 patients with a DD diagnosis (62.5 % female), 131 (11.8 %) patients were diagnosed with an additional SMD, and 69 (6.2 %) were diagnosed with cognitive impairment. DD-SMD patients were on average 10 years younger and had longer time between first mental healthcare contact and DD disorder than DD patients. DD-CI patients were on average 10 years older and had a higher proportion of females. Paliperidone (21.9 %) and aripiprazole (20.6 %) were the modal antipsychotic drugs chosen overall. DD-SMD patients were more likely to receive paliperidone and to be prescribed long-acting injectable medication; DD-CI were more likely to receive risperidone or quetiapine; and DD patients were more likely to receive olanzapine. ConclusionsSociodemographic and clinical characteristics and choice of antipsychotic drug and delivery method for individuals with DD vary based on its comorbidity.

Monitoring the Effectiveness of Treatment in Women with Schizophrenia: New Specialized Cooperative Approaches.

Women with schizophrenia have specific health needs that differ from those of men and that change through successive life stages. We aimed to review the biopsychosocial literature on schizophrenia that addresses clinically important questions related to the treatment of women, including somatic morbi-mortality, hyperprolactinemia, comorbid substance use disorders, social risk factors, and medication effectiveness/safety. Data search terms were as follows: (Morbidity AND mortality) OR hyperprolactinemia OR ("substance use disorders" OR addictions) OR ("social risk factors") OR ("drug safety" OR prescription) AND women AND schizophrenia. A secondary aim was to describe a method of monitoring and interdisciplinary staff strategies. Schizophrenia patients show an increased risk of premature death from cardiovascular/respiratory disease and cancer compared to the general population. The literature suggests that close liaisons with primary care and the introduction of physical exercise groups reduce comorbidity. Various strategies for lowering prolactin levels diminish the negative long-term effects of hyperprolactinemia. Abstinence programs reduce the risk of victimization and trauma in women. Stigma associated with women who have serious psychiatric illness is often linked to reproductive functions. The safety and effectiveness of antipsychotic drug choice and dose differ between men and women and change over a woman's life cycle. Monitoring needs to be multidisciplinary, knowledgeable, and regular.

Functional Changes of Orexinergic Reaction to Psychoactive Substances.

It is becoming increasingly apparent the importance of the central nervous system (CNS) as the major contributor to the regulation of systemic metabolism. Antipsychotic drugs are used often to treat several psychiatric disorders, including schizophrenia and bipolar disorder However, antipsychotic drugs prescription, particularly the second-generation ones (SGAs), such as clozapine and olanzapine, is related to a considerable weight gain which usually leads to obesity. The aim of this paper is to assess the influence of orexin A on sympathetic and hyperthermic reactions to several neuroleptic drugs. Orexin A is a neuropeptide which effects both body temperature and food intake by increasing sympathetic activity. Orexin A-mediated hyperthermia is reduced by haloperidol and is blocked by clozapine and olanzapine. Orexin A-mediated body temperature elevation is increased by risperidone. These hyperthermic effects are delayed by quietapine. In this paper, it is discussed the orexinergic pathway activation by neuroleptic drugs and its influence on human therapeutic strategies. With the aim to determine that neuroleptic drugs mediate body temperature control through to the orexinergic system, we summarized our previously published data. Psychiatric disorders increase the risk of developing metabolic disorders (e.g., weight gain, increased blood pressure, and glucose or lipid levels). Therefore, the choice of antipsychotic drug to be prescribed, based on the relevant risks and benefits of each individual drug, has an essential role in human health prevention.

The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis

BackgroundAntipsychotics have serious metabolic side effects on blood glucose. However, the comparative influence of these drugs on blood glucose levels has not been comprehensively evaluated. We conducted a network meta-analysis to create a hierarchy of the side effects of 12 antipsychotic drugs on changes in blood glucose levels.MethodsA systematic search of the PubMed, EMBASE and Cochrane databases (last search June 2016) was conducted to identify studies that reported randomized controlled trials (RCTs) comparing changes in blood glucose levels between patients receiving one of 12 antipsychotic drugs or a placebo for the treatment of schizophrenia or related disorders. The studies we searched were limited to those published in English. Two reviewers independently extracted data. The primary outcome of interest was changes in fasting glucose levels.ResultsWe included 47 studies with 114 relevant arms. Of the antipsychotic drugs, only olanzapine was associated with significantly increased glucose levels compared to a placebo (mean difference (MD) = 3.95, 95% confidence interval (CI) = 0.14 to 7.76). Moreover, olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone (MD = 5.51, 95% CI = 1.62 to 9.39), lurasidone (MD = 5.58, 95% CI = 0.53 to 10.64) or risperidone (MD = 3.05, 95% CI = 0.87 to 5.22). Ziprasidone and lurasidone were associated with minimal glucose changes compared to the other antipsychotics.ConclusionsOlanzapine was associated with a significantly greater change in blood glucose levels than ziprasidone, lurasidone, risperidone or placebo treatment. The application of a hierarchy of glucose metabolism-related side effects may help clinicians tailor the choice of antipsychotic drug to meet the needs of individual patients.

Physical Health and Drug Safety in Individuals with Schizophrenia.

While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context. Prescribers are encouraged to use the lowest effective dose and to avoid the routine use of multiple antipsychotics. Scheduled monitoring of body mass index, waist circumference, blood pressure, glucose, lipids, prolactin, electrocardiograms, and extrapyramidal symptoms is recommended. Lifestyle interventions are recommended to mitigate antipsychotic-induced weight gain. Prescribers should follow Canadian guidelines on the treatment of obesity, dyslipidemia, and diabetes. Recommendations on antipsychotic drug choice are made for users particularly concerned about extrapyramidal symptoms. Careful monitoring and attention by prescribers may mitigate adverse effects associated with antipsychotic medications.

A Review of the Psychiatric Care Provided to Patients who Subsequently Offended

Background : An examination (audit) of the files of patients who had received any mental health services in the year prior to an alleged offence may inform our understanding of the relationship between mental health and crime. More helpfully, it may provide information to facilitate a reduction in the rate of such tragic events Method : The records of all patients assessed by the Midland Regional Forensic Psychiatric service in the 26 months from January 2010 were screened. The 222 who received a diagnosis of a non-organic psychosis and who were recorded as having offended within one year of a previous psychiatric service attendance formed the cohort. The data extracted from their clinical files, relating primarily to that pre-offence psychiatric contact, included legal, clinical and contextual information. Results : Analysis examined the characteristics of this forensic population and most particularly, of their pre-offending service contact. This identified clinical practice and delivery issues which could reduce the rate of conversion of psychiatric patients to “forensic” status. Conclusions : The results inform issues of effectiveness of adult service delivery with particular consideration of the intensity of clinical contact, antipsychotic drug choice and adherence and the use of assertive treatment.

Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis

The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. None.

GENDER DIFFERENCES IN PREMORBID, ENTRY, TREATMENT, AND OUTCOME CHARACTERISTICS IN A TREATED EPIDEMIOLOGICAL SAMPLE OF 661 PATIENTS WITH FIRST EPISODE PSYCHOSIS

The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs.We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation.We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73–1·03; amisulpride 0·66, 0·53–0·78; olanzapine 0·59, 0·53–0·65; risperidone 0·56, 0·50–0·63; paliperidone 0·50, 0·39–0·60; zotepine 0·49, 0·31–0·66; haloperidol 0·45, 0·39–0·51; quetiapine 0·44, 0·35–0·52; aripiprazole 0·43, 0·34–0·52; sertindole 0·39, 0·26–0·52; ziprasidone 0·39, 0·30–0·49; chlorpromazine 0·38, 0·23–0·54; asenapine 0·38, 0·25–0·51; lurasidone 0·33, 0·21–0·45; and iloperidone 0·33, 0·22–0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from −0·09 for the best drug (haloperidol) to −0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to −1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to −0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses.Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines.None.

C.15.05 Schizophrenia: antipsychotics in the acute phase and beyond

The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs.We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation.We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73–1·03; amisulpride 0·66, 0·53–0·78; olanzapine 0·59, 0·53–0·65; risperidone 0·56, 0·50–0·63; paliperidone 0·50, 0·39–0·60; zotepine 0·49, 0·31–0·66; haloperidol 0·45, 0·39–0·51; quetiapine 0·44, 0·35–0·52; aripiprazole 0·43, 0·34–0·52; sertindole 0·39, 0·26–0·52; ziprasidone 0·39, 0·30–0·49; chlorpromazine 0·38, 0·23–0·54; asenapine 0·38, 0·25–0·51; lurasidone 0·33, 0·21–0·45; and iloperidone 0·33, 0·22–0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from −0·09 for the best drug (haloperidol) to −0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to −1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to −0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses.Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines.None.

Shared Decision Making and Long-Term Outcome in Schizophrenia Treatment

Compliance with antipsychotic medication is a major issue in schizophrenia treatment, and noncompliance with antipsychotic treatment is closely related to relapse and rehospitalization. An enhanced involvement of patients with schizophrenia in treatment decisions ("shared decision making") is expected to improve long-term compliance and reduce rehospitalizations. The aim of the present analysis was to study whether shared decision making (SDM) in antipsychotic drug choice would influence long-term outcome. From February 2003 to January 2004, psychiatric state hospital inpatients with a diagnosis of schizophrenia (ICD-10; N = 107) were recruited for the trial using a cluster-randomized controlled design. An SDM program on antipsychotic drug choice consisting of a decision aid and a planning talk between patient and physician was compared with routine care with respect to long-term compliance and rehospitalizations (6-month and 18-month follow-up). On the whole, we found high rates of noncompliance and rehospitalization. There were no differences between intervention and control groups in the univariate analyses. However, when controlling for confounding factors in a multivariate analysis, there was a positive trend (p = .08) that patients in the SDM intervention had fewer rehospitalizations. Additionally, a higher desire of the patient for autonomy and better knowledge at discharge were associated with higher hospitalization rates. The intervention studied showed a positive trend but no clear beneficial effect on long-term outcomes. A more thorough implementation of SDM (e.g., iterative administration of decision aid) might yield larger effects. Those patients with higher participation preferences are at higher risk for poor treatment outcomes and therefore require special attention. Strategies to match these patients' needs might improve compliance and long-term outcomes.

Sertindole: efficacy and safety in schizophrenia

Sertindole is an antipsychotic drug with affinity for dopamine D2, serotonin 5-HT2A and 5-HT2C, and α1-adrenoreceptors. Preclinical studies suggest that sertindole acts preferentially on limbic and cortical dopaminergic neurons and clinical trials have confirmed that sertindole is effective at a low dopamine D2 occupancy level. The active substance has a long half-life. Oral administration once daily yields highly stable plasma levels. These features may explain the clinically observed low frequency of extrapyramidal side effects, including tardive dyskinesia. In contrast to most antipsychotics, sertindole seems to be void of sedative effects. However, although not strictly proven by objective neuropsychological tests, this asset of sertindole does not add to the cognitive problems inherent in schizophrenia. Administration of sertindole is more often associated with prolongation of QTc compared with most other currently used antipsychotics. However, large cohort analyses do not suggest that all-cause mortality is higher with sertindole than with, for example, risperidone or olanzapine. The effective antipsychotic dose range of sertindole is 12 – 20 mg/day, with small variations among patients. The frequency of most adverse events, for example extrapyramidal symptoms and somnolence, with such a dose does not differ from placebo. Three side effects have been more common than with placebo/haloperidol in short-term studies: weight gain, rinithis and a decreased ejaculation volume. Two head-to-head comparisons (one in treatment-resistant patients) of sertindole and risperidone showed equivalent effects on positive symptoms. For negative symptoms, one study obtained equivalent effects and one a superior effect of sertindole. Sertindole should not be used as first-line treatment for first-episode patients with schizophrenia because of the QTc prolongation. It has a side-effect profile that makes it an interesting alternative for many patients who do not respond well to the initial choice of antipsychotic drug.

How do psychiatrists choose among different antipsychotics?

We attempted to determine the decision rules psychiatrists use in the choice of antipsychotic drugs for inpatients with schizophrenia. Interviews were conducted with 50 hospital psychiatrists in Southern Germany. Each physician was interviewed with respect to the reasons for his antipsychotic drug choice in the cases of three patients with a diagnosis of schizophrenia. Interviews were audiotaped and subsequently analyzed using a standardized coding scheme. The clinical decision rules identified are highly complex, with a mean of eight categories cited per patient. Categories named included the patient's past treatment response, side effects, intended route of administration and co-morbidities. Moreover, psychiatrists strongly take the patient's target symptoms and the assumed efficacy of certain compounds into account in their choice of medication. Psychiatrists' explanations for their antipsychotic drug choice seem for the most part reasonable and overlap substantially with drug-choice algorithms of clinical guidelines. However, psychiatrists additionally use indicators that--in their view--might predict treatment response. For these indicators, which are derived from personal experience, it is still unclear whether they are valid and simply have not yet been proven in clinical trials or whether they merely represent unfounded assumptions on the part of the doctors.

Patients' perceptions of their involvement in decision making about antipsychotic drug choice as outlined in the NICE guidance on the use of atypical antipsychotics in schizophrenia

Introduction: The NICE technology appraisal for atypical antipsychotics in patients with schizophrenia recommends that prescribers and patients should make the choice of antipsychotic drug jointly. In order to make an informed choice, patients must feel that they have been given sufficient information. The aim of this study was to survey patients' perceptions of the information they had been given about their medication and whether they felt that they had been given a choice with respect to the medication they received.Methods: We approached 100 outpatients with a known diagnosis of schizophrenia who attended one of three clinics in Oxleas NHS trust. Questions were asked about the information they had received about their medication and whether they felt that they had been given a choice. Patient demographic details were also collected.Results: Eighty-four patients consented to be interviewed. Fifty-four (64%) were happy with the medication prescribed for them but 47 (56%) felt that they had not received enough information about their medication. Twenty (24%) of these patients were not concerned as they felt happy to trust their doctor. There was a trend towards patients prescribed typical antipsychotics being more likely to have unmet information needs (p = .062). Those prescribed atypicals were more likely to have participated in agreeing a relapse plan (p = .016). Information needs varied widely.Discussion: Patients perceive the information they receive about antipsychotic drugs as being suboptimal. Without information, true informed choice is impossible. It is difficult to see how the information needs of all patients can be met without patients and carers taking a more active role in questioning prescribers. Written copies of standard questions could be made available as prompts to facilitate this process.Declaration of interest: None.

P.2.047 Shared decision making on antipsychotic drug choice for inpatients with schizophrenia

P.2.047 Shared decision making on antipsychotic drug choice for inpatients with schizophrenia

Binding of antipsychotic drugs to human brain receptors: Focus on newer generation compounds

Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (K ds) for nine new antipsychotic drugs (iloperidone, melperone, olanzapine, ORG 5222, quetiapine, risperidone, sertindole, ziprasidone, and zotepine), one metabolite of a new drug (9-OH-risperidone), and three older antipsychotics (clozapine, haloperidol, and pimozide) at nine different receptors (α 1-adrenergic, α 2-adrenergic, dopamine D 2, histamine H 1, muscarinic, and serotonin 5-HT 1A, 5-HT 1D, 5-HT 2A, and 5-HT 2C receptors). Iloperidone was the most potent drug at the two adrenergic receptors. ORG 5222 was the most potent drug at dopamine D 2 and 5-HT 2c receptors, while ziprasidone was the most potent compound at three serotonergic receptors (5-HT 1A, 5-HT 1D, and 5-HT 2A). At the remaining two receptors, olanzapine was the most potent drug at the histamine H 1 receptor (K d=0.087 nM); clozapine at the muscarinic receptor (K d=9 nM). Certain therapeutic and adverse effects, as well as certain drug interactions can be predicted from a drug's potency for blocking a specific receptor. These data can provide guidelines for the clinician in the choice of antipsychotic drug.