Meta-analysis of Total Effect Decomposition in the Presence of Multiple Mediators: The Example of Schizophrenia Treatment.

BACKGROUND: Causal mediation analysis addresses mechanistic questions by decomposing and quantifying effects operating through different pathways. Because most individual studies are underpowered to detect mediating effects, we outlined a parametric approach to meta-analyzing causal mediation and interaction analyses with multiple mediators, compared it with a bootstrap-based alternative, and discussed its limitations. METHODS: We employed fixed- and random-effects multivariate meta-analyses to integrate evidence on treatment-mediators and mediators-outcome associations across trials. We estimated path-specific effects as functions of meta-analyzed regression coefficients; we obtained standard errors using the delta method. We evaluated the performance of this approach in simulations and applied it to assess the mediating roles of positive symptoms of schizophrenia and weight gain in the treatment effect of paliperidone ER on negative symptoms across four efficacy trials. RESULTS: Both simulations and the application showed that the meta-analytic approaches increased statistical power. In the application, we observed substantial mediating effects of positive symptoms (proportions mediated from fixed-effects meta-analysis: (Equation is included in full-text article.)). Weight gain may have beneficial mediating effects; however, such benefit may disappear at high doses when metabolic side effects were excessive. CONCLUSIONS: Meta-analyzing causal mediation analysis combines evidence from multiple sources and improves power. Targeting positive symptoms may be an effective way to reduce negative symptoms that are challenging to treat. Future work should focus on extending the existing methods to allow for more flexible modeling of mediation.

The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms: An analysis of the CATIE schizophrenia trial.

Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS-), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between -2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (-2.66 points; 95% CI: -4.98, -0.35), PANSS- (-1.59; 95% CI: -4.31, 1.14), and total PANSS (-6.11; 95% CI: -13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.

The role of PANSS symptoms and adverse events in explaining the effects of paliperidone on social functioning: a causal mediation analysis approach.

To date, no study has evaluated the joint role of symptoms and adverse events as mediators of the effect of second-generation antipsychotics on patients' social functioning. We used recently developed methods for mediation analysis with multiple mediators to clarify the interplay of adverse events and symptoms in explaining the effects of paliperidone (R code for implementing the mediation analysis for multiple mediators is provided). We used data from 490 participants in a 6-week randomized dose-response trial that assigned three fixed dosages of ER OROS paliperidone (3, 9, and 15 mg/day). The primary outcome was an individual's score on the social performance scale assessed after 6 weeks. The sum of Positive and Negative Syndrome Scale (PANSS), weight gain, and extrapyramidal symptoms measured via the Simpson-Angus Scale after 5 weeks were investigated as potential mediators and effect modifiers of treatment effects. Results from mediation analyses showed that the improvements in social functioning are partly explained by reduction in PANSS symptoms. Suggestive evidence that adverse events could play a role as mediators was found. In particular, weight gain displayed a non-linear relationship with social functioning, whereby beneficial effects observed at small levels of weight gain were reduced in the presence of excessive weight gain. In conclusion, we found that the short-term effects of paliperidone on social functioning were dependent on the successful reduction in PANSS symptoms and possibly the occurrence of excessive weight gain, thus suggesting future directions for treatment and interventions.

Factors associated with length of psychiatric hospitalization.

OBJECTIVE: Criteria for psychiatric hospitalization have undergone marked changes. Efforts to limit length-of-hospitalization risk greater morbidity at discharge and increased needs for appropriate aftercare. Accordingly, we evaluated factors associated with length of psychiatric hospitalization and aftercare-types. METHODS: We reviewed medical records of 589 patients with major psychiatric disorders hospitalized in a university-affiliated, not-for-profit psychiatric hospital to identify characteristics associated with length of hospitalization, types of aftercare and insurance coverage, using standard bivariate and multivariate analytical methods. RESULTS: Notable factors associated with longer hospitalization included: more highly supervised aftercare, diagnosis of schizophrenia or schizoaffective>affective disorders, longer illnesses, higher antipsychotic doses and more complex drug-treatments at discharge, lower GAF functional status, unemployment, being unmarried, as well as public vs. private insurance. Multivariate modeling sustained association of longer hospitalization with higher antipsychotic doses, more structured aftercare, public insurance, lower GAF scores, and diagnoses of chronic psychotic disorders. Structured aftercare was associated with younger age, fewer years ill, and private insurance, but varied little by diagnosis and was unrelated to ethnicity. Public insurance was associated notably with being unemployed, unmarried, less functional, having a chronic psychotic disorder for more years, and lack of structured aftercare. CONCLUSIONS: Illness severity and functional impairment may modulate efforts to limit psychiatric hospitalization. Higher-level aftercare was associated with illness and disability factors as well as with private insurance; public insurance was associated with dysfunction, unemployment and chronic illness, as well as longer hospitalization.

Metabolic syndrome in psychiatrically hospitalized patients treated with antipsychotics and other psychotropics.

OBJECTIVE: We evaluated prevalence and risk factors for metabolic syndrome in inpatients treated with antipsychotics, with or without other psychotropic drugs. Although the literature on metabolic syndrome in psychiatry has expanded in recent years, we seek to elucidate some of the remaining gaps by examining a severely and chronically ill population heavily treated with pharmacological agents. METHODS: With data from medical records of 589 adults hospitalized at McLean Hospital in 2010 and 2011, we used standard statistical analyses to characterize risks and covariates of metabolic syndrome. RESULTS: With prior antipsychotic treatment, prevalence of metabolic syndrome was 29.5%. The syndrome was strongly associated with being overweight (≥25 kg/m(2) in 60.1% of subjects), older age, longer treatment-exposure, schizoaffective diagnosis (39.8%), more illness-episodes or hospitalizations, polytherapy, and higher total daily chlorpromazine-equivalent doses, but not sex. Notably, metabolic syndrome risk was greater among young, antipsychotic treated patients (15.5-fold at age ≤25 years). CONCLUSIONS: The findings extend information on the association of metabolic syndrome with antipsychotic treatment. Metabolic syndrome was found in 30% of antipsychotic-exposed inpatients. Risk was surprisingly high in young persons and after brief treatment-exposure, and psychotropic polytherapy increased risk.

Marijuana impacts mood in bipolar disorder: a pilot study.

Patients with bipolar disorder (BP) often report subjective mood improvements after smoking marijuana (MJ); however, empirical studies supporting this claim have not been conducted. We conducted this study to determine if marijuana has an impact on mood in bipolar patients who smoke marijuana (MJBP), hypothesizing MJBP participants would experience improved mood after smoking MJ. All participants completed electronic mood ratings three times daily and recorded episodes of MJ use using Palm Pilot devices in their own environments in order to examine the impact of MJ use on mood in MJ-smoking bipolar patients (n = 12) and pure MJ smokers (MJ; n = 20). Difference scores were calculated between pre and post-MJ scales. Patients with BP (n = 11) who did not smoke MJ were also included as a comparison group. Significant mood improvement was observed in the MJBP group on a range of clinical scales after smoking MJ, while the MJ group reported a slight worsening of symptoms. Notably, total mood disturbance, a composite of the Profile of Mood States, was significantly reduced in the MJBP group, but increased in the MJ group after smoking. Further, while the MJBP group reported generally worse mood ratings than the BP group prior to smoking MJ, they demonstrated improvement on several scales post-MJ use as compared to BP participants. These data provide empirical support for anecdotal reports that MJ acts to alleviate mood-related symptoms in at least a subset of bipolar patients and underscore the importance of examining MJ use in this population.

Pilot randomized, controlled trial of pramipexole to augment antipsychotic treatment.

The preferential dopamine D(3)-agonist pramipexole (4.25±0.38 mg/day) or placebo were added for up to 12 weeks to ongoing antipsychotic treatment for 24 adult patients with DSM-IV schizophrenia or schizoaffective disorder. Pramipexole was generally well-tolerated (82% trial-completion), and yielded greater decreases in PANSS-total scores (drug/placebo=2.1; p=0.04), with similar decreases in PANSS positive and negative scores and 6.7-fold greater reduction of serum prolactin concentrations compared to placebo. There were no differences in ratings of mood, cognition or extrapyramidal symptoms, all of which were low at intake.

Use of mood stabilizers for hospitalized psychotic and bipolar disorder patients.

Treatments given to patients with primary psychotic disorders include mood stabilizers (MSs) combined with other psychotropics, despite the limited evidence of efficacy, safety, and lack of regulatory approval. We analyzed records of 636 inpatients at the McLean Hospital (2002-2009), who were diagnosed with bipolar disorder (n=318), a schizoaffective disorder (n=210), or schizophrenia (n=108), to evaluate MS-usage, drug-selections, combinations and doses, improvement, adverse-effect risks, associated factors, and secular trends. Between 2002 and 2009, the use of MSs increased from 53 to 94% of patients, MSs per patient increased by 74%, and the total final doses (lithium-equivalents in milligrams/day) increased by 35%. The most commonly prescribed MSs ranked: valproate, lithium, lamtogrine. With the use of MSs, the duration of hospitalization was longer by an average of 18%, Clinical Global Impression ratings improved by 55%, and adverse-effects risk was lower by 22%. In multivariate logistic modeling, treatment with a MS was associated with: (i) most recent year of sampling, (ii) more psychotropics per patient at discharge, (iii) diagnosis (schizophrenia < schizoaffective or bipolar disorders), (iv) longer period of hospitalization, and (v) somewhat younger age. MSs, usually in combination with antipsychotics, were used increasingly for inpatients over the past decade, including for patients with primary psychotic disorders. The effectiveness and safety of this practice remain to be evaluated adequately.

International consensus study of antipsychotic dosing.

OBJECTIVE: Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated. METHOD: With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances. RESULTS: Participants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal function, illness stage and severity, sex, and diagnosis, were associated with dosing modifications. CONCLUSIONS: In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials.

Changes in medication practices for hospitalized psychiatric patients: 2009 versus 2004.

BACKGROUND: We tested the hypothesis that combinations and total daily doses of psychotropics for hospitalized patients diagnosed with major psychiatric disorders are rising. METHODS: We evaluated McLean Hospital records of 481 consecutive inpatients with DSM-IV schizophrenia, schizoaffective, or bipolar disorders in 2004 (n = 278) or 2009 (n = 203) to compare characteristics and treatments. RESULTS: In 2009, Clinical Global Impression (CGI)-severity scores were 6% lower at intake and improved 1.7 times more than in 2004, as hospitalization-length decreased by 12%. Polytherapy (> or = 2 psychotropics) increased in 2009 (affective or schizoaffective disorders > schizophrenia). Total psychotropics/patient (3.1-3.2) remained stable but mood-stabilizers/patient increased markedly and antipsychotics/patient decreased somewhat in 2009. Antipsychotic-choice (2009) ranked: quetiapine, aripiprazole, risperidone, and others; mood-stabilizers ranked: lamotrigine, valproate, lithium, and others (1/4 off-label). In 2009, final total antipsychotic doses (mg/day) increased by 97%, and mood-stabilizers by 75%. Adverse-effect rates fell by half. Factors differing independently for 2009 versus 2004 ranked: (a) more CGI improvement, (b) more mood-stabilizers/patient, (c) lower admission CGI scores, and (c) higher total antipsychotic dose. COMMENT: Combinations and doses of antipsychotic and mood-stabilizing drugs for inpatients increased markedly (2004 vs. 2009) without consistent correspondence of agents/person and doses, without apparent increase in major adverse effects, and with possibly superior clinical improvement.

Health and economic burden of metabolic comorbidity among individuals with bipolar disorder.

OBJECTIVES: To compare the prevalence and health care costs of metabolic conditions in patients with bipolar disorder to age- and sex-matched control patients using a large insurance claims database. METHODS: A retrospective analysis of medical service and prescription claims from the Thomson Reuters (Healthcare) MarketScan Commercial Database (which includes claims information on >12 million employees with employer-based insurance and their dependents in the United States) was conducted. Claims data for 28,531 patients with bipolar disorder were compared for 1 year with data for 85,593 age- and sex-matched control patients with no mental health disorders and no psychotropic medication use. RESULTS: Patients with bipolar disorder had a significantly higher prevalence of metabolic comorbidities than the general population (37% vs 30%, P < 0.0001), and annual medical service treatment costs for metabolic conditions were twice that of the control cohort (531 dollars vs 233 dollars, P < 0.0001). The bipolar cohort had significantly higher overall medical service and prescription drug costs than those of the control cohort (12,764 dollars vs 3,140 dollars, P < 0.0001). Prescription medication costs for metabolic conditions were higher as well, with bipolar cohort per-patient costs of 571 dollars versus 301 dollars for the control cohort (P < 0.0001). CONCLUSIONS: Patients with bipolar disorder have significantly more metabolic comorbidities and higher medical costs than age- and sex-matched controls. Studies that link claims data with medical records or primary data collection pertaining to metabolic conditions may overcome limitations in the diagnostic information and outcome predictors. To reduce the medical and economic burden of bipolar disorder, strategies should be identified to prevent the development of metabolic comorbidities and improve medication adherence.

Comparison of mania patients suitable for treatment trials versus clinical treatment.

It remains uncertain whether bipolar disorder (BPD) patients in randomized-controlled trials (RCTs) are sufficiently representative of clinically encountered patients as to guide clinical-therapeutic practice. We complied inclusion/exclusion criteria by frequency from reports of 21 RCTs for mania, and applied them in a pilot study of patients hospitalized for DSM-IV BPD manic/mixed states to compare characteristics and clinical responses of patients who did versus did not meet exclusion criteria. From 27 initially identified inclusion/exclusion criteria ranked by citation frequency, we derived six inclusion, and 10 non-redundant-exclusion factors. Of 67 consecutive patients meeting inclusion criteria, 15 (22.4%) potential "research subjects" met all 10 exclusion criteria. The remaining 52 "clinical patients" differed markedly on exclusion criteria, including more psychiatric co-morbidity, substance abuse, involuntary hospitalization, and suicide attempts or violence, but were otherwise similar. In both groups responses to clinically determined inpatient treatments were similar, including improvement in mania ratings. Based on applying reported inclusion/exclusion criteria for RCTs to a pilot sample of hospitalized-manic patients, those likely to be included in modern RCTs were similar to patients who would be excluded, most notably in short-term antimanic-treatment responses. The findings encourage further comparisons of subjects included/excluded from RCTs to test potential clinical generalizability of research findings. The pilot study is limited in numbers and exposure times with which to test for the minor differences between "research subjects" and "clinical patients."

Hospital use of antipsychotic drugs: polytherapy.

OBJECTIVE: Growing acceptance of new psychotropic drugs encouraged a survey of current use of antipsychotic drugs alone and in combinations, with comparisons with previous findings. METHOD: Records from a random sample of McLean Hospital (Belmont, Mass) inpatients treated with an antipsychotic from March to May 2004 were reviewed for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, discharge diagnosis; all current psychotropic drug treatments; initial, peak, and final chlorpromazine-equivalent milligram-per-day dose of antipsychotics (APD); initial, peak, and final lithium-equivalent dose (milligram per day) of mood stabilizers (MS); weight change; clinical status at admission and discharge; and days of hospitalization. RESULTS: In the 305 inpatients sampled (n = 184 women, 60.3%), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, clinical conditions ranked as follows: major affective (n = 161, 52.8%), psychotic (n = 99, 32.5%), and other disorders (n = 45, 14.8%). Modern drugs comprised 92% of antipsychotic prescriptions, and quetiapine (usually at low doses) was most frequently prescribed. "Polytherapy" (simultaneous treatment with > or =2 psychotropic agents) at discharge was identified in 80% of antipsychotic-treated patients. Use of at least 2 antipsychotics (in 23% of cases) was associated with a 2.8-fold increase in total dose vs monotherapy (651 +/- 403 vs 232 +/- 205 mg/d). Total antipsychotic doses also were higher with mood stabilizer (most often divalproex) or sedative (usually high-potency benzodiazepine) cotreatment, use of older neuroleptics, psychotic-disorder diagnoses, and substance use comorbidity. Polytherapy was not associated with superior clinical improvement or shorter hospitalization but was associated with higher body weight. CONCLUSIONS: Polytherapy involving antipsychotic drugs continues to increase despite limited empirical evidence for greater effectiveness or of safety of such combinations.

An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenia/schizoaffective disorder.

OBJECTIVE: To determine the effect of intramuscular (IM) olanzapine in severely agitated patients. METHODS: This was an open-label multicenter 1-week observational study of IM olanzapine treatment in severely agitated inpatients and psychiatric emergency services with bipolar mania (n = 22) or schizophrenia (n = 52). Mean change from baseline to 2 h post-first injection (LOCF) in agitation was assessed by PANSS-Excited Component (PANSS-EC) (score range: 5-35 points) mean change from baseline to 15, 30, 45, 60, 90, and 120 min post-first injection, and visit-wise mean changes from mixed-model repeated measures analysis of variance. Kaplan-Meier survival curve analyses estimated time to categorical response (rating of

Lithium treatment reduces suicide risk in recurrent major depressive disorder.

OBJECTIVE: Evidence that clinical treatment reduces suicide risk in major depressive disorder (MDD) is limited and inconsistent. Since lithium shows major antisuicidal effects in bipolar disorders and in heterogeneous mood disorder samples, we evaluated evidence of antisuicidal effects of lithium in patients with recurrent MDD. DATA SOURCES: We searched MEDLINE (January 1966 to April 2006; search terms: lithium, suicide, affective disorder, depression, major depression, and mood disorder) for studies reporting suicides or suicide attempts during treatment with and without lithium in recurrent MDD patients, and we added data for 78 new subjects, provided from the Lucio Bini Mood Disorders Research Center in Sardinia, Italy. Suicide rates were pooled and analyzed by use of incidence-rate ratios (IRRs) and meta-analytic methods. DATA SYNTHESIS: Eight studies involved 329 MDD patients and exposure for 4.56 years (1149 person-years) with, and 6.27 years (1285 person-years) without, lithium. Overall risk of suicides and suicide attempts was 88.5% lower with vs. without lithium: 0.17%/y versus 1.48%/y (IRR = 8.71; 95% CI: 2.10 to 77.2, p = .0005); for completed suicides (85% risk reduction), IRR = 6.77 (95% CI: 1.29 to 66.8, p = .01). Meta-analysis by risk difference and risk ratio supported these findings, and sensitivity analysis yielded similar results with studies omitted serially. CONCLUSIONS: This is the first meta-analysis suggesting antisuicidal effects of lithium in recurrent MDD, similar in magnitude to that found in bipolar disorders.

Clinical outcome in patients with bipolar I disorder, obsessive compulsive disorder or both.

BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive (OCD) and other anxiety disorders, but the impact of such comorbidity on long-term outcome has not been evaluated systematically. METHODS: Extensive follow-up assessments were carried out at 4.3 years after index hospitalizations in a mixed BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20) alone. RESULTS: At follow-up, ratings of functional status were similar across groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9-times more frequent among comorbid than OCD patients. OCD symptoms averaged 150% more severe in OCD than comorbid subjects, and were not measured in BPD subjects. CONCLUSIONS: Despite potential sampling bias with previously hospitalized subjects, the findings suggest that comorbid BPD-OCD patients may be clinically more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not negatively impact the long-term clinical outcome.

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002.

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

BACKGROUND: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. METHODS: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. RESULTS: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. CONCLUSIONS: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Antipsychotic drug use: McLean Hospital, 2002.

OBJECTIVE: Major changes in antipsychotic treatment in recent years encouraged a survey of inpatient practice in 2002, compared with earlier samples. METHODS: Based on records of a random sample of McLean Hospital inpatients prescribed antipsychotics in 2002, the study recorded DSM-IV discharge diagnosis, all psychotropic treatments and doses, initial, peak and final doses of all antipsychotics, clinical status at admission and discharge, and adverse effects reported. Results were compared with similar data from our earlier surveys. RESULTS: Subjects were 344 inpatients (n = 202 women, 59%), diagnosed with psychotic (n = 102, 30%), bipolar (n = 93, 27%), major depressive (n = 67, 19.5%), dementia (n = 19, 5.5%), substance-use (n = 28, 8%) or other psychiatric disorders (n = 35, 10%). Second-generation antipsychotics accounted for 88% of antipsychotic prescriptions; 17% of patients received > or = 2 antipsychotics and total CPZ-eq discharge does in 2002 averaged 291 +/- 305 mg/day (22% less than a 1998 peak). Doses were unrelated to age, but higher in men, among psychotic vs major affective disorder patients, and with greater illness-severity and longer hospitalization. There was a 3.3-fold increase in the simultaneous use of > or = 3 psychotropic agents since 1998. CONCLUSIONS: The use of second-generation antipsychotics dominates current inpatient practice. Total antipsychotic dosing has not increased recently, but the use of multiple psychotropics increased strikingly from 1998 to 2002.