title: Olanzapine versus haloperidol in the treatment of schizoaffective disorder. Acute and long-term therapy. Fluvoxamine-Controlled Release Formulation for the Treatment of Generalized Social Anxiety Disorder Does switching to a new antipsychotic improve outcomes?: Data from the CATIE Trial Efficacy of valproate versus lithium in mania or mixed mania: a randomized, open 12-week trial Is flunarizine a long-acting oral atypical antipsychotic? A randomized clinical trial versus haloperidol for the treatment of schizophrenia. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. A 6-month, multicenter, open-label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Mirtazapine versus amitriptyline in the long‐term treatment of depression: a double‐blind placebo‐controlled study Antidepressant-related adverse effects impacting treatment compliance: Results of a patient survey. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram. Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study. Atypical and Conventional Antipsychotic Drugs in Treatment-Naive First-Episode Schizophrenia: A 52-Week Randomized Trial of Clozapine Vs Chlorpromazine Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. Selective Serotonin Reuptake Inhibitor Discontinuation: Side Effects and Other Factors That Influence Medication Adherence Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. A Double-Blind Placebo-Controlled Study of Controlled Release Fluvoxamine for the Treatment of Generalized Social Anxiety Disorder Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia Oxcarbazepine versus Divalproex Sodium for the Continuing Treatment of Mania Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. Attitudes about Antidepressants: Influence of Information about Weight-Related Side Effects An Evaluation of Monitoring Practices in Patients on Second Generation Antipsychotics A multicentre placebo‐controlled trial comparing the efficacy of mianserin and chlordiazepoxide in general practice patients with primary anxiety Weight changes with depot neuroleptic maintenance therapy Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. Impact of lamotrigine and lithium on weight in obese and nonobese patients with bipolar I disorder. Long-term efficacy and safety of aripiprazole in patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder: 26-week prospective study. Atypical antipsychotic monitoring in the Kilkenny Mental Health Services.
abstract: BACKGROUND The effectiveness of antipsychotic monotherapy in  schizoaffective disorder  is limited , and further constrained by safety concerns . AIMS We aim ed to compare the efficacy , tolerability and safety profile of the new pharmaceutical , olanzapine , with haloperidol . METHOD Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospect i ve international study . Subjects were r and omly allocated to six weeks of olanzapine ( 5 - 20 mg ) or haloperidol ( 5 - 20 mg ) treatment ; responders were followed for up to one year of double-blind , long-term maintenance therapy . RESULTS Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy , including clinical response . Significantly fewer olanzapine patients left the study early , and fewer adverse events were observed among those receiving olanzapine . During maintenance , olanzapine-treated patients continued to experience additional improvement , with fewer EPS but more weight gain than those on haloperidol . CONCLUSIONS Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder Background : Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships , as well as work performance . We report the results of a multicenter , r and omized , placebo-controlled trial comparing the efficacy , safety , and tolerability of fluvoxamine controlled release ( CR ) to placebo in patients with generalized social anxiety disorder . Methods : A total of 279 adult patients meeting all inclusion /exclusion criteria was recruited at 23 United States sites and r and omly assigned to receive either fluvoxamine CR ( 100 - 200 mg/d ) or placebo for 12 weeks . The dose could be increased , based on efficacy and tolerability , in increments of 50 mg/d at weekly intervals . The dosage remained constant during weeks 6 to 12 . Results : Treatment with fluvoxamine CR result ed in statistically and clinical ly significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement , and at week 6 on the Sheehan Disability Scale , Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale . The most frequent adverse events reported by patients on fluvoxamine CR were headache , nausea , somnolence , and insomnia . No weight gain was observed for either treatment group , and at end point , there were no differences between treatments on overall sexual function , as measured by the Arizona Sexual Experience Scale . Conclusions : Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder PURPOSE Previous analysis of data from CATIE showed that patients r and omly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to r and omization . This study addresses additional outcomes measures evaluating symptoms , neurocognition , quality of life , neurological side effects , weight , and health costs . First , considering patients r and omized to olanzapine or risperidone  , outcomes among patients who had been on the drug to which they were r and omized prior to CATIE ( N=129 " stayers " ) were compared to outcomes of those who switched to either of these two drugs ( N=269 " switchers " ) . A second set of analyses considered patients on baseline monotherapy with olanzapine ( N=297 ) ; risperidone ( N=252 ) or quetiapine ( n=87 ) and compared those r and omly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE . In mixed models of each outcome the independent variable of primary interest represented stay vs. switch , with multivariate adjustment for potential confounding factors . RESULTS With one exception , there were no significant differences between stayers and switchers on any outcome measure in either set of analyses . The exception was that , in the second set of analyses , patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs . CONCLUSION Switching to a new medication yielded no advantage over staying on the previous medication . Staying on olanzapine was associated with greater weight gain The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode . This international , r and omized , open-label , parallel-group , equivalence study included 268 patients with bipolar I disorder . The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day . Treatment duration was 12 weeks . The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end . Secondary outcome measures were response and remission rates , change in Montgomery and Åsberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score , and occurrence of adverse events . The mean change from baseline in Young Mania Rating Scale score was 15.8±5.3 in the lithium group and 17.3±9.4 in the valproate group . The 90 % confidence interval of the intergroup difference ( −0.69 ; 3.31 ) was within prespecified equivalence limits . Response rates were 72.6 % in the lithium group and 79.5 % in the valproate  group . Remission rates were 58.5 and 71.9 % , respectively . No intergroup differences were observed in median time to treatment response ( 21 days ) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Åsberg Depression Rating Scale scores . Adverse events were reported in 42.8 % of patients in the lithium group and 41.5 % in the valproate group . Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks BACKGROUND Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine , vertigo , and cognitive deficits related to cerebrovascular disorders . Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics . However , its clinical antipsychotic efficacy has never been investigated . OBJECTIVE To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in out patients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder . METHOD Seventy patients from 2 centers were r and omly assigned and participated in a double-blind , parallel-group , flexible-dose study comparing flunarizine ( 10 - 50 mg/day ) and haloperidol ( 2.5 - 12.5 mg/day ) for 12 weeks . Patients were assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Improvement ( CGI-I ) scale , the Extrapyramidal Symptom Rating Scale ( ESRS ) , a battery for cognitive performance , and laboratory examinations . The study was conducted from September 2004 to May 2007 . RESULTS Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol . Both groups showed significant symptom improvement during the study , with a reduction of 21 % in the flunarizine group and 19 % in the haloperidol group in PANSS total scores ( p < .05 ) . There were no significant differences in PANSS overall score and all subscales , CGI-I score , or cognitive performance . Dropout rates , ESRS scores , and prolactin levels were not different between groups , but significantly more patients reported emergence of akathisia in the haloperidol group ( p = .04 ) , and weight gain was significantly higher with flunarizine ( 1.2 kg ) than with haloperidol ( -0.8 kg ) ( p < .05 ) . CONCLUSION This is the first study evaluating the antipsychotic properties of flunarizine , which showed good efficacy and tolerability for the treatment of schizophrenia , with a possible atypical profile . Its unique pharmacokinetic profile as an oral drug with long half-life ( 2 - 7 weeks ) , low cost , and low induction of extrapyramidal symptoms warrants further investigation , particularly in psychiatric patients with low adherence to treatment OBJECTIVE The goal of this 5-year naturalistic study of patients treated with clozapine  was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors , including weight gain , lipid abnormalities , age , clozapine dose , and treatment with valproate . METHOD Data on age , gender , race , diagnosis , family history of diabetes , and age at clozapine initiation were collected from medical records of 82 out patients with schizophrenia or schizoaffective disorder .  Clozapine dose , data on use of valproate , and laboratory test results were recorded at 6-month intervals . RESULTS The mean age at the time of clozapine initiation of the 82 patients was 36.4 years ; 26.8 % of the patients were women , and 91.5 % were Caucasian . The mean baseline weight was 175.5 lb , and the mean body mass index was 26.9 kg/m(2 ) . Thirty patients ( 36.6 % ) were diagnosed with diabetes during the 5-year follow-up . Weight gain , use of valproate , and total daily dose of clozapine  were not significant risk factors for developing diabetes mellitus . Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine . There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level . CONCLUSIONS The results support the hypotheses that patients treated with clozapine  experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes BACKGROUND Carbamazepine is frequently used for treating bipolar disorder , but few large trials have assessed its efficacy in preventing relapse . We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules ( ERC-CBZ ; SPD417 ) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes . METHOD A 6-month , open-label study enrolled 92 patients with DSM-IV bipolar disorder ( most recent episode : 67 % [ N = 62 ] mixed , 33 % [ N = 30 ] manic ) who had participated in 2 previous 3-week , double-blind , placebo-controlled studies . Subjects received beaded ERC-CBZ ( 200 - 1600 mg/day ) , titrated at investigators ' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse , and secondary efficacy measures included Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions scale ( CGI ) , and Hamilton Rating Scale for Depression ( HAM-D ) scores . Data were gathered from January 2000 to January 2002 . RESULTS Of 77 patients analyzed in the intent-to-treat population , 11 ( 14.3 % ) relapsed . Fifty-three patients ( 68.8 % ) discontinued early , including 18 ( 23.4 % ) due to adverse events . Observed mean time to relapse was 61.1 days , while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days . Improvements on the YMRS , CGI , and HAM-D from the beginning of prior double-blind treatment were maintained . The most common adverse events were headache , dizziness , and rash . No significant weight gain was noted . CONCLUSION We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial . Adverse events were generally mild to moderate and were typical of those associated with carbamazepine . Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder A double-blind controlled study comparing the effects of bupropion to doxepin in out patients with primary depression was conducted to evaluate efficacy and safety differences between the two drugs . Following a 7-day placebo washout period , patients could be treated for up to 13 weeks on either treatment . Antidepressant response was assessed by the Hamilton Depression and Anxiety Scales , Clinical Global Severity and Improvement Ratings , and the Zung Self-Rating Depression Scale . Comparable efficacy between the compounds was found across the 13-week study . Doxepin differed from bupropion mainly on the sleep factor of the Hamilton Depression Scale , with doxepin improving sleep to a greater extent than bupropion . Doxepin produced a greater incidence of anticholinergic side effects , including dry mouth , constipation , sleepiness , and tiredness , in comparison to bupropion . Also , increased appetite and weight gain were consistent side effects of doxepin relative to bupropion OBJECTIVE The authors ' goal was to compare the efficacy and tolerability of 6 months ' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder . METHOD Brief Psychiatric Rating Scale ( BPRS ) scores and Clinical Global Impression ( CGI ) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study . RESULTS Comparable improvements in BPRS and CGI severity scores were seen with both drugs . Olanzapine produced significant increases from acute- study baseline values in weight and body mass index and within-group increases in total cholesterol , low-density lipoprotein cholesterol , and fasting insulin . Between-group differences were not significant for lipids and insulin . Mean QTc values at endpoint were 407.1 msec ( baseline mean=406.0 msec ) and 394.4 msec ( baseline mean=399.7 msec ) for ziprasidone and olanzapine , respectively . No patient had a QTc interval > or = 500 msec . CONCLUSIONS Ziprasidone and olanzapine had comparable long-term efficacy ;  olanzapine was associated with significant weight gain and metabolic alterations Of 580 patients r and omly assigned to short-term , double-blind treatment with either mirtazapine , amitriptyline or placebo , a total of 217 patients clinical ly judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study  ( mirtazapine , n = 74 ; amitriptyline , n = 86 and placebo , n = 57 ) . The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data . Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo ( p < 0.05 ) , and a significantly longer time to relapse was shown on the survival analysis . There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks , with fewer patients relapsing . There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis ( p < 0.05 ) . The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks . At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response , Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms , but there was no difference from placebo in the proportion of patients with sustained response .  Mirtazapine was well tolerated with a side-effect profile similar to that of placebo . The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain . Objective ly measured weight gain was more frequent with amitriptyline ( 22 % of patients ) compared with mirtazapine ( 13 % of patients ) . Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo , in particular sedative and anticholinergic side effects . The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression , which on some measures showed an advantage compared with amitriptyline , coupled with its improved side-effect profile , commends this antidepressant for the long-term treatment of depression BACKGROUND Despite the high prevalence of depression in the United States , 10 few studies have identified which adverse effects ( AEs ) patients are willing or unwilling to tolerate when receiving antidepressants . OBJECTIVE The aim of this study was to identify reasons for discontinuation10 and noncompliance with antidepressant medications , the impact of AEs on compliance and quality of life ( assessed using impact of AEs on activities of daily living ) , and patients ' suggestions for improving their medication , using a patient survey . METHODS Patients aged 18 to 65 years with mild to severe depression were 10 r and omly selected by their physicians to be sent an invitation to complete the 42- question survey . Three hundred physicians nationwide assessed the severity of depression and symptoms of anxiety in each respondent , using their judgment . Patients were asked specific questions to assess reasons for discontinuation/noncompliance . Patients were also asked to rate AEs based on how difficult they were to " live with , " and what 2 aspects of their antidepressant medication they would change if they could . RESULTS In a separate , concurrent study , physicians classified 175 ( 50 % ) abd Results :0 mildly to moderately depressed and 84 ( 24 % ) as severely depressed . Ninety-one respondents ( 26 % ) were classified as having symptoms of anxiety . Two hundred seven patients ( 60 % ) indicated they had discontinued treatment with an antidepressant agent at some point in their lives , the most common reason for which was lack of efficacy ( 92 patients [ 44 % ] ) . Of the 344 patients currently being treated with an antidepressant , 75 ( 22 % ) reported noncompliance . The most common reasons for noncompliance were " have trouble remembering to take it " ( 19/44 patients [ 43 % ] ) , " gained a lot of weight " ( 11/41 [ 27 % ] ) , " unable to have an orgasm " ( 8/40 [ 20 % ] ) , and " lost interest in sex " ( 8/41 [ 20 % ] ) . The 4 AEs patients expressed as " extremely difficult to live with " were " weight gain " ( 104 patients [ 31 % ] ) , " unable to have erection " ( 83 [ 25 % ] ) , " difficulty reaching orgasm " ( 80 [ 24 % ] ) , and " tired during the day/no energy " ( 69 patients [ 21 % ] ) . The 3 most frequently cited improvements patients ( n = 327 ) would make to their medications were better efficacy ( 176 patients [ 54 % ] ) and eliminating AEs related to sexual desire and weight gain ( 112 [ 34 % ] and 105 [ 32 % ] patients , respectively ) . CONCLUSIONS The findings of this survey of patients with mild to severe10 depression suggest that compliance , and hence efficacy , can be promoted by ( 1 ) underst and ing what patients expect and desire from the antidepressants they are prescribed and ( 2 ) prescribing antidepressants associated with low rates of weight gain , sexual dysfunction , or tiredness BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day in elderly patients with major depression according to DSM-IV criteria . METHODS A r and omised , double-blind , parallel group 6-month study . Efficacy was assessed by MADRS , CGI Global Improvement , CGI Severity of Illness and GDS-20 scores and safety by physical examinations , vital signs , adverse events and UKU side effect rating . Plasma levels of venlafaxine , its major metabolite O-desmethylvenlafaxine and citalopram were followed . RESULTS One hundred and fifty-one male and female patients ( 64 - 89 years ) were enrolled and 118 patients completed the study . Comparable improvements in MADRS , CGI Severity of Illness , CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment . The MADRS remission rate was 19 % for venlafaxine and 23 % for citalopram .  Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment . There were no clinical ly significant changes in blood pressure or body weight . CONCLUSION The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects . Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram AIM Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia .  Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors . There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies . To clarify the clinical traits of perospirone in the treatment of schizophrenia , the clinical efficacies and side-effects of perospirone and risperidone were compared in a r and omized clinical multicenter trial . METHODS Sixty-six schizophrenia patients were enrolled in the trial . The Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale ( DIEPSS ) scores were investigated at 0 , 4 , 8 and 12 weeks . RESULTS Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups , with no significant between-group differences at 4 and 12 weeks . Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8 . There were no significant differences in the DIEPSS scores at 0 , 4 , 8 and 12 weeks between the perospirone and risperidone groups . The numbers of patients who dropped out did not differ between the perospirone and risperidone groups . CONCLUSIONS Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia . Both antipsychotic agents were equally well-tolerated The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects  than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients  receiving CLZ or CPZ  that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission BACKGROUND The safety and efficacy of the first long-acting injectable atypical antipsychotic , risperidone , were assessed in stable patients with schizophrenia switched from oral antipsychotic medications . METHOD Data were collected between July 1 , 2001 , and October 25 , 2002 . The study population included patients from clinics , hospitals , and physicians ' offices . After a 4-week run-in period , symptomatically stable patients with schizophrenia ( DSM-IV ) who had been taking haloperidol ( N = 46 ) , quetiapine ( N = 45 ) , or olanzapine ( N = 50 ) received 25 mg of long-acting risperidone . The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone . Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter , open-label study . RESULTS Long-acting risperidone was well tolerated . Of the 141 patients who participated in the study , the most frequently reported adverse events were insomnia ( 16 % ) , headache ( 15 % ) , psychosis ( 11 % ) , and agitation ( 11 % ) . The mean increase in body weight was 0.4 kg . No other clinical ly relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment . Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone . Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale ( PANSS ) scores at week 8 ( -2.5 , p < .01 ) and week 12 ( -3.9 , p < .001 ) . At endpoint , 37 % ( 50/135 ) of these stable patients were rated as clinical ly improved ( > or = 20 % decrease in PANSS total scores ) . CONCLUSIONS Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated . Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia Objective : Patients with major depression discontinue taking their antidepressants for many reasons . Although side effects are often cited as the reason for discontinuation , few prospect i ve studies have addressed this question , and none has specifically examined discontinuation in patients with severe depression . Method : In patients and out patients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission . Three months later , patients were contacted and interviewed to determine antidepressant usage and the side effects experienced , including when these were experienced and their severity . Results : Between October 2001 and April 2003 , 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up . One in 4 patients discontinued the index antidepressant . Among specific side effects noted , only " change in weight " and " anxiety " were significant predictors of discontinuation after controlling for confounders . Experiencing 1 or more " extremely " bothersome side effects was associated with more than a doubling of the risk of discontinuation , but the presence of side effects and side effects less severe than " extremely " bothersome were not significant predictors . There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates . Conclusion : The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested . Disparate findings from earlier studies may reflect aspects of study design , such as examining population s whose severity of depression varied widely or not controlling for important confounding factors . Future research should separately examine high-risk groups ( or control for severity of depression ) and carefully rule out other potential contributors to discontinuation OBJECTIVE This 52-week r and omized , double-blind , flexible-dose , multicenter study evaluated the overall effectiveness ( as measured by treatment discontinuation rates ) of olanzapine , quetiapine , and risperidone in patients early in the course of psychotic illness . METHOD Patients were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) administered in twice-daily doses . Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks ( primary outcome measure ) based on a prespecified noninferiority margin of 20 % . RESULTS A total of 400 patients were r and omly assigned to treatment with olanzapine ( N=133 ) , quetiapine ( N=134 ) , or risperidone ( N=133 ) . The mean modal prescribed daily doses were 11.7 mg for olanzapine , 506 mg for quetiapine , and 2.4 mg for risperidone . At week 52 , all-cause treatment discontinuation rates were 68.4 % , 70.9 % , and 71.4 % for olanzapine , quetiapine , and risperidone , respectively . Reductions in total score on the Positive and Negative Syndrome Scale ( PANSS ) were similar for the three treatment groups , but reductions in PANSS positive subscale scores were greater in the olanzapine group ( at 12 weeks and at 52 weeks or withdrawal from study ) and the risperidone group ( at 12 weeks ) . The most common elicited adverse events for olanzapine were drowsiness ( 53 % ) , weight gain ( 51 % ) , and insomnia ( 38 % ) ; for quetiapine , drowsiness ( 58 % ) , increased sleep hours ( 42 % ) , and weight gain ( 40 % ) ; and for risperidone , drowsiness ( 50 % ) , menstrual irregularities in women ( 47 % ) , and weight gain ( 41 % ) . CONCLUSIONS Olanzapine , quetiapine , and risperidone demonstrated comparable effectiveness in early-psychosis patients , as indicated by similar rates of all-cause treatment discontinuation Abstract : This was a r and omized double-blind placebo-controlled multicenter study to assess the efficacy , safety , and tolerability of fluvoxamine in a controlled release ( CR ) formulation for treatment of generalized social anxiety disorder ( GSAD ) . A total of 300 subjects with GSAD were r and omly assigned to receive either fluvoxamine CR ( N = 149 ) or placebo ( N = 151 ) for 12 weeks . Mean changes from baseline to end point in Liebowitz Social Anxiety Scale ( LSAS ) , Clinical Global Impression Severity of Illness Scale ( CGI-S ) , Sheehan Disability Scale ( SDS ) , as well as the mean end point scores in Clinical Global Impression Improvement Scale ( CGI-I ) and Patient Global Impression of Improvement Scale ( PGI ) were compared between the fluvoxamine CR and placebo treatment groups . Arizona Sexual Experience Scale ( ASEX ) , adverse event , and other safety parameters were also assessed . The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score ( primary measure ) starting at week 4 . At end point , there was a mean change from baseline of −36.1 ± 2.7 ( 37 % reduction ) in the LSAS total score in the fluvoxamine CR group compared with −27.3 ± 2.4 ( 28 % reduction ) in the placebo group ( P = 0.020 for mean change ) . Fluvoxamine CR was also significantly superior to placebo in SDS , CGI-S , CGI-I at end point ( secondary measures ) . When compared with placebo , fluvoxamine CR did not cause any significant weight gain or clinical ly significant sexual dysfunction as measured by ASEX . In summary , fluvoxamine CR is an efficacious , safe , and well-tolerated treatment of generalized social anxiety disorder Clozapine has been the gold st and ard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities . This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia . The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication . This 18-week , r and omized , double-blind , parallel study compared treatment with either olanzapine ( 5 - 25 mg/day , n=75 ) or clozapine ( 100 - 500 mg/day , n=72 ) in patients with schizophrenia who were nonresponsive to , or intolerant of , st and ard acceptable antipsychotic therapy . At the 18-week endpoint , no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used : Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative , or general psychopathology or Clinical Global Impression severity ( CGI-S ) . Response rates based on the criteria of Kane et al. [ Arch . Gen. Psychiatry 45 ( 1988 ) 789 ] were also not significantly different between olanzapine-treated ( 57.9 % ) and clozapine-treated patients ( 60.8 % ) . There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography , and no clinical ly and statistically significant changes were seen in vital signs or laboratory measures in either group . Both treatments were well tolerated . Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy ( treatment resistance ) or intolerable side effects ( treatment intolerance ) . Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia Background and objective Oxcarbazepine , an antiepileptic and a derivative of carbamazepine , has been shown to have clinical utility as an antimanic agent . This study sought to assess the efficacy and tolerability of oxcarbazepine compared with divalproex sodium in the treatment of patients with mania . Patients and methods 57 patients from a large clinical practice who had recently begun treatment with divalproex sodium  were r and omly assigned to one of two treatment groups . In this open-label , single (rater)-blind study , group 1 remained on treatment with divalproex sodium and group 2 was switched to oxcarbazepine . Both treatment groups were followed for 10 weeks after the switch . Pharmacotherapeutic efficacy was compared using the Clinician Administered Rating Scale for Mania ( CARS-M ) . Weight and adverse events were monitored throughout the study . Results 83 % of patients using oxcarbazepine showed a decrease in mania as assessed using the CARS-M , and 70 % showed a net decrease in weight over the 10-week course of the study . For the divalproex sodium group , 53 % showed a decrease in mania , as assessed by CARS-M , and 37 % lost weight . Conclusion Oxcarbazepine showed comparable efficacy to divalproex sodium , yet appeared to do so with an equal or more benign side-effect profile , particularly with regard to weight . These results suggest that oxcarbazepine , which has been used in Europe for the treatment of mood disorders for some time ( albeit used off-label for this purpose ) may show promise for use in the US as an agent for maintenance of non-acute mania BACKGROUND Weight change and the weight-related health factors of nonfasting serum glucose , serum cholesterol , and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years , and comparisons were made to patients treated with haloperidol .  Baseline body mass index ( B BMI ; kg/m2 ) and dose ( mg/day ) were investigated as predictors of long-term weight change experienced during olanzapine treatment . METHOD This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients r and omly assigned 2:1 to either olanzapine , 5 to 20 mg/day , or haloperidol , 5 to 20 mg/day . After 6 weeks of acute therapy , patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy . RESULTS Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg ( 13.8 lb ) and a median of 5.90 kg ( 13.0 lb ) . This was significantly higher than that for haloperidol-treated patients , whose mean weight gain was 0.69 kg ( 1.5 lb ) after 1.15 years ( p < .001 ) . Patients with higher B BMI ( > 27.6 ) gained significantly less weight during treatment with olanzapine than their lighter counterparts ( B BMI < 27.6 ) ( p < .001 ) . The effect of olanzapine dose on weight was not significant ( p > or = . 183 ) . Median serum glucose at endpoint was not significantly associated ( p = .096 ) with weight change for olanzapine .  Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically ( p < or = .001 ) but not clinical ly significant . The difference in incidence of elevated serum glucose , cholesterol , or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different ( p > .05 ) . CONCLUSION Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years . Higher B BMI was predictive of a lower long-term weight gain , while dose was not a significant predictor of greater longer term weight change . The relationship between weight change and glucose was not statistically significant . The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinical ly relevant based on the ranges observed Antidepressant drugs are frequently prescribed for women and have various side effects , including potential effects on body weight . This experiment examined the effects of information about the weight-related side effects of antidepressants on  women 's attitudes toward the drugs . 60 college women were r and omly assigned to read about one of two drugs , fluoxetine ( Prozac ) or Imipramine ( Tofranil ) . Participants were either told or not told about veridical weight-related side effects , namely , weight loss for Prozac and weight gain for Tofranil . As hypothesized , weight-gain information lowered the personal acceptability of Tofranil , and weight-loss information enhanced the acceptability of Prozac . Although research with clinical population s is required , undergraduate women 's decisions about the use of antidepressant medications may be influenced by societal body-image ideals Objective : Treatment with second generation antipsychotics ( SGAs ) can increase the risk of patients with schizophrenia developing obesity , hyperlipidaemia and diabetes . Routine monitoring is recommended , but clinical practice suggests monitoring is not conducted at a rate necessary for these comorbidities . The aim was to audit what proportion of patients were having their weight , height , girth , body mass index , lipids and blood sugar levels monitored and recorded . Method : An audit of patients with schizophrenia , discharged from three psychiatric wards , was conducted . Two data sheets were recorded for every patient and inter-rater reliability was calculated . Data were then entered into SPSS and statistical significance calculated . Results : The sample consisted of 93 patients ; SGAs were taken by 31 % of admitted and 88 % of discharged patients . Of these , 65 % had their weight recorded , 61 % height , 31 % r and om blood sugar levels , 3 % postpr and ial blood sugar levels , 2 % glycosylated haemoglobin , and 7.5 % cholesterol and triglycerides . Girth and BMI were not recorded . Abnormalities were detected in 29 % of recorded BSL and 2 % of recorded cholesterol . Conclusions : Patients with schizophrenia on antipsychotics  have an alarmingly low rate of monitoring of these common adverse effects and comorbidities . Clinicians need to be aware of this , so that they can improve their practice In a double‐blind multicentre trial in general practice , 144 patients with primary anxiety received daily treatment with mianserin or chlordiazepoxide , 30‐60 mg , or placebo . There were no statistically significant differences in efficacy between the three treatments in the 106 patients who completed the 6‐week trial . However , there was a substantial trend in favour of mianserin ( P= 0.1 ) , but not chlordiazepoxide , over placebo as assessed by the difference in overall improvement on the Hamilton Anxiety Scale . This trend may be clinical ly significant since more patients dropped out from the placebo group because of lack of effect or deterioration than did from the active treatment groups , particularly during the latter part of the trial A prospect i ve study of schizophrenic patients prescribed injectable depot neuroleptic drugs as maintenance therapy showed a clinical ly significant weight gain in 55 % of patients . No significant difference was shown between flupenthixol decanoate and fluphenazine decanoate , nor was a clinical ly meaningful relationship shown with dose , or the use of anti‐parkinsonian drugs . The weight gain continued for at least 2 years following a mental state relapse . It is suggested that the monitoring of weight and giving of appropriate advice on diet are two essentials in maintenance therapy of chronic schizophrenia OBJECTIVE To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence . METHOD A post hoc analysis of a r and omized , double-blind , 8-week , fixed-dose study comparing olanzapine 10 , 20 , and 40 mg/day for patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) with suboptimal response to current treatment ( N = 599 ) was conducted between September 12 , 2003 , and November 3 , 2005 , at 55 study centers in the United States . Nonadherence was defined as not taking medication as prescribed based on daily pill counts . Because there was no significant difference in nonadherence between dose groups , effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined . Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence . RESULTS During the 8-week study , 34.5 % of patients were nonadherent at least once . Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score ( -22.57 vs. -26.84 , p = .002 ) . Longer duration of nonadherence was associated with reduced likelihood of treatment response ( odds ratio = 0.94 , 95 % CI = 0.90 to 0.99 , p = .008 ) . The early treatment discontinuation rate was higher in nonadherent compared to adherent patients ( 40.8 % vs. 24.5 % , p < .001 ) . Adherent and nonadherent patients had comparable outcomes in most safety measures , except for weight change , for which adherent patients had greater weight gain than nonadherent patients ( 2.63 kg vs. 1.96 kg , p = .02 ) . Greater depression severity at baseline ( p = .01 ) and greater hostility level during the study were significant risk factors for nonadherence ( p = .02 ) . CONCLUSIONS Medication nonadherence had a significantly negative impact on treatment response , highlighting the importance of adherence to achieve satisfactory treatment outcome . Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00100776 OBJECTIVE This study assessed weight changes in a large cohort of patients with bipolar disorder who were treated with r and omly assigned maintenance monotherapies . METHOD A post hoc analysis was conducted to assess the effects of lamotrigine , lithium , and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind , placebo-controlled , 18-month studies . RESULTS Mean changes in weight among obese patients ( N=155 ) at week 52 were -4.2 , + 6.1 , and -0.6 kg with lamotrigine , lithium , and placebo , respectively ( lamotrigine versus lithium and lithium versus placebo ) . Among nonobese patients ( N=399 ) , mean changes in weight ( kg ) at week 52 were -0.5 , + 1.1 , and + 0.7 with lamotrigine , lithium , and placebo , respectively , with no significant differences among groups . CONCLUSIONS Obese patients with bipolar I disorder lost weight while taking lamotrigine and gained weight while taking lithium AIMS To date there have been no reports of long-term efficacy of aripiprazole in Asian population s. The aim of the present study was therefore to investigate the long-term efficacy , safety and tolerability of aripiprazole in a large number of patients with schizophrenia , schizophreniform disorder , or schizoaffective disorder in Korea . METHODS This study was a prospect i ve , multicenter , single-group , 26-week open study of patients with schizophrenia , schizophreniform disorder , or schizoaffective disorder . A total of 300 Korean patients participated in the study . The primary efficacy measure was the Positive and Negative Syndrome Scale ( PANSS ) total score , and secondary efficacy measures included the PANSS positive and negative subscales , Clinical Global Impression-Severity of Illness ( CGI-S ) . Tolerability and safety were assessed by monitoring the frequency and severity of treatment-emergent adverse events , extrapyramidal symptoms ( EPS ) , vital signs , weight , and laboratory tests . RESULTS Aripiprazole produced rapid and significant improvements on all efficacy measures . As evidence d by PANSS total score , PANSS positive subscales and the CGI-S scores , first-episode drug-naive patients demonstrated significantly greater efficacy relative to patients who had previously experienced one or more episodes of relapse . Aripiprazole was associated with significant decrease of serum prolactin level . The subjects showed mild weight gain . CONCLUSION Aripiprazole is an effective antipsychotic in the long-term treatment of both positive and negative symptoms . This study extends the findings of previous long-term studies , and has found that there is no significant difference with regard to ethnicity in response to aripiprazole OBJECTIVES To examine baseline testing and ongoing monitoring of cardiovascular and other risk factors in individuals prescribed atypical antipsychotic medications . METHODS We derived a list of baseline and ongoing monitoring tests from the literature ( Weight , BMI , blood pressure , U&E , LFTs , glucose , HbA1C , FBC , TFTs , prolactin , lipids & ECG ) and then review ed a r and om sample of 80 records of patients prescribed atypical antipsychotics and currently attending an Irish public catchment area service , for evidence of testing . RESULTS Levels of testing for baseline tests ranged from 45 % for blood pressure to 0 % for BMI . Levels of ongoing monitoring tests ranged from 42.5 % for U&E to 0 % for BMI . Patients admitted to hospital were much more likely to have had testing . CONCLUSIONS The need for baseline and ongoing monitoring of certain tests in patients prescribed atypical antipsychotics is increasingly accepted . Levels of such testing are currently quite low and need to increase
target: We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts .
  There were few discrepancies between published evidence and the expert panel in ranking these drugs .
  Conclusion Potential for weight gain is an important consideration in choice of any psychotropic .
  This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices
background: Introduction Psychotropic medication use is associated with  weight gain .
  While there are studies and review s comparing weight gain for psychotropics within some classes , clinicians frequently use drugs from different classes to treat psychiatric disorders .
  Objective To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence -based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics .