Antipsychotic medication and smoking prevalence in acutely hospitalized patients with chronic schizophrenia

The atypical antipsychotic, clozapine, has been reported to reduce smoking in schizophrenic patients. We sought to determine whether other atypical antipsychotics would also be associated with a decreased prevalence of smoking in this population. Data were obtained from three groups of chronic, hospitalized, schizophrenic patients, receiving either a typical antipsychotic (n=15), clozapine (n=6), or another atypical antipsychotic (n=18). In addition to smoking prevalence, the groups were compared with regard to demographics (age, education), medication (doses, duration of treatment, side-effects), clinical (diagnosis, duration of illness) and behavioral (Wide-Range Achievement Test, Wechsler Adult Intelligence Scale) variables. Smoking prevalence differed significantly among the three groups (P<0.001). Clozapine was associated with a significantly lower incidence of smoking than either typical drugs (P<0.003) or other atypical antipsychotics (P=0. 042). The groups did not differ on demographic or other medication variables or on any of several behavioral measures. However, a diagnosis of paranoid schizophrenia was also significantly correlated with smoking (P<0.01), but not with medication class. Although the cause is still unknown, these results are consistent with reports that clozapine reduces smoking and provide new data on smoking prevalence associated with other atypical agents.     

Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment

Objective To examine prevalence of movement disorders (MDs) such as tardive dyskinesia (TD), parkinsonism or akathisia in an adolescent population with schizophrenia and in relationship to predominantly atypical antipsychotic treatment. Method Ninety-three patients (aged 19.6±2.2 years) were ascertained in this cross-sectional/retrospective study. 76 patients (81.7%) received atypical, 10 (10.8%) typical antipsychotics and 7 (7.5%) combinations of atypical/typical antipsychotics. MD symptoms were assessed using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS). Results Movement disorder symptoms were found in 37 patients (39.8%) fulfilling strict/subthreshold criteria for TD (5.4/11.8%), parkinsonism (2.2/25.8%) or akathisia (1.1/11.8%), respectively. Patients treated with typical antipsychotics displayed a significantly higher EPS-score (P=0.036) and a tendency towards a higher BAS-score (P=0.061) compared to patients with atypical antipsychotics. Treatment durations with typical/atypical antipsychotics showed trends towards advantages of atypical antipsychotics with regard to parkinsonism/akathisia symptoms (P=0.061; P=0.054), but not with regard to TD symptoms (P=0.003), possibly due to confounding effects. Conclusion Under treatment with atypical antipsychotics MD symptoms are less prevalent and less pronounced than under typical antipsychotics. We speculate that the finding of relatively high prevalence rates of subthreshold MD symptoms may be, at least partially, explained by previous or combined therapy with typical antipsychotics.     

Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

Background

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.

Methods

We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration.

Results

In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.

Conclusion

Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.     

Hyperlipidemia in persons using antipsychotic medication: a general population-based birth cohort study

BACKGROUND: Shortly after phenothiazines were introduced, they were found to elevate serum triglyceride and total cholesterol levels. During the past decade, an increasing body of literature has also documented this effect in atypical antipsychotics. Previous studies of antipsychotic-associated hyperlipidemias are based on clinical samples, mostly from case series. We studied the prevalence of hyperlipidemia in subjects who did and did not take antipsychotic medication in a prospective, general population-based birth cohort. METHOD: The study sample consisted of 5654 members of the unselected Northern Finland 1966 Birth Cohort who participated in the 1997-1998 clinical examination at 31 years of age. Blood samples were taken after an overnight fast, and serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were determined. Health habits and other possible correlates for hyperlipidemia were assessed using a questionnaire. The sample was analyzed in 4 categories according to use of antipsychotic medication: (1) atypical, (2) typical, (3) atypical and typical (for the 3 antipsychotic categories, total N = 45), and (4) no antipsychotic medication (N = 5609). Nonparametric tests and multiple logistic regression analysis were used to measure the effect of antipsychotics on serum lipids. RESULTS: High lipid levels were found in persons treated with both atypical and typical medication (mean total cholesterol = 233 mg/dL, mean triglycerides = 163 mg/dL). Mean total cholesterol and triglycerides were also high in subjects who used only typical medication (215 mg/dL and 148 mg/dL, respectively). The prevalence of hypercholesterolemia, high LDL cholesterol, and hypertriglyceridemia was high in persons using antipsychotic medication (31.1%, 20.0%, and 22.2%, respectively) compared with persons not using such medication (12.2%, 10.2%, and 7.0%, respectively). After we adjusted for risk factors for hyperlipidemia (sex, diet, waist circumference, physical exercise, smoking, and alcohol consumption), the results of logistic regression analysis showed that in persons treated with antipsychotic medication the risk of hypercholesterolemia was 2.8 (95% CI = 1.4 to 5.6); of hypertriglyceridemia, 2.3 (95% CI = 1.0 to 5.4); and of high LDL cholesterol, 1.6 (95% CI = 0.7 to 3.5). CONCLUSION: Lipid levels in subjects who used both atypical and typical medication and those who used only typical medication were high even in young age. As these persons are at special risk of hyperlipidemia, their lipid levels should be regularly monitored, and a cholesterol-lowering diet, as well as medication, should be considered. The results indicate an elevated risk of hyperlipidemia in persons using antipsychotic medication independent of the other risk factors assessed.     

Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. OBJECTIVES: To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. METHODS: We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. RESULTS: Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53-0.86] for lithium, 0.68 (95% CI = 0.55-0.85) for lamotrigine, and 0.82 (95% CI = 0.57-1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49-0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35-0.79 and RR = 0.37; 95% CI = 0.24-0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46-0.91 and RR = 0.40; 95% CI = 0.20-0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34-0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12-2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08-3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31-3.70). There were few data for carbamazepine or medications given as adjunct therapy. CONCLUSIONS: Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.     

Heart rate variability in schizophrenic patients switched from typical antipsychotic agents to amisulpride and olanzapine. 3-month follow-up

Schizophrenia is a severe mental disorder that requires lifelong treatment, and therefore information on the cardiovascular safety and tolerance of antipsychotics is of significant clinical importance. Atypical antipsychotics have been used to treat schizophrenia patients since the 1990s, and more and more patients have been switched to these from typical antipsychotics; however, there is still no accessible evaluation tool for assessing cardiovascular safety. In this study, we used a computer-assisted 5-min measurement of resting heart rate variability (HRV) in schizophrenia patients who were switched to atypical antipsychotic agents (amisulpride and olanzapine) due to severe side effects (tardive dyskinesia). In 15 patients who switched to amisulpride and 18 to olanzapine, HRV was evaluated before the medication was switched, and patients were followed up every month for 3 months after the switch. Frequency-domain analyses of short-term and stationary respiratory rate (RR) intervals were performed to evaluate low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). Our results showed significant increases in the mean, variance and HF of RR intervals in the amisulpride group, but not in the olanzapine group. These results indicate that amisulpride has a more vagotonic effect, suggesting greater cardiovascular safety as compared with olanzapine when subjects are switched from typical antipsychotic agents.     

Assessing the utility of atypical antipsychotic medication in adults with mild mental retardation and comorbid psychiatric disorders

OBJECTIVE: Research on psychiatric outcomes among individuals dually diagnosed with mild mental retardation and co-occurring mental illness who are treated with antipsychotic medication is markedly limited due to difficulties encountered in (1) making valid and reliable psychiatric diagnoses and (2) accurately rating and following psychiatric symptom change over time in this specialty population. METHOD: To address these issues, DSM-IV psychiatric diagnoses were made by an experienced dual-diagnosis clinician, and the Aberrant Behavior Checklist (ABC) and the Global Assessment of Functioning were used to assess behavioral and psychiatric features in a psychiatric partial hospital setting. Data were collected by chart review from 72 patients admitted consecutively from January 1998 to December 1999. Assessments were compared at admission and discharge in this retrospective study for 3 treatment groups that were defined by antipsychotic medication status at discharge: no antipsychotic (N = 15), atypical antipsychotic only (N = 41), and mixed atypical/typical antipsychotics or typical anti-psychotic only (N = 16). RESULTS: Improvement on the ABC social withdrawal subscale was greater for atypical anti-psychotic medication-treated, dually diagnosed patients than for those who received other treatment regimens. In addition, a dose-response relationship was observed for this subscale and atypical antipsychotic medication dose. CONCLUSION: For certain psychotic patients with mild mental retardation, the atypical antipsychotics may be an appropriate and effective treatment modality.     

Atypical antipsychotics and risk of cerebrovascular accidents

OBJECTIVE: Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly. METHOD: The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts-users of typical antipsychotics, risperidone, and olanzapine-were identified and compared. RESULTS: Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4 (95% CI=0.7-2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.     

Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: a two-year prospective study.

BACKGROUND: Antipsychotics are widely used to manage behavioral disorders in patients with dementia. Recently, serious concerns have been raised about the stroke and mortality risk of atypical antipsychotics when administered to patients with dementia. AIM: The aim of this study was to examine the impact of atypical and conventional antipsychotics on mortality and hospital admissions among Finnish elderly institutionalized patients with dementia in a two-year follow up and to compare their prognosis with that of nonusers. PATIENTS AND METHODS: The authors examined 254 very frail patients with dementia, mean age 86 years, from seven Finnish nursing homes and two hospitals in 1999-2000. Medical records provided information on the use of daily antipsychotic medication; central registers confirmed mortality for up to two years. RESULTS: Nearly one-half (48.4%) of the patients used antipsychotic medication: 37.4% received conventional neuroleptics (N = 95) and 11.0% received atypical antipsychotics (N = 28). The mean number of hospital admissions was higher among the nonusers than among the users of conventional or atypical antipsychotics. Of the users of atypical antipsychotics (risperidone, olanzapine), 32.1% died within 2 years. The respective figures for users of conventional neuroleptics were 45.3%, and for the nonusers, 49.6%. In the Cox proportional hazard model, a high number of medications and the use of physical restraint predicted higher mortality at two years. The use of atypical antipsychotics showed lower risk of mortality, if any. The respective test for conventional antipsychotics was nonsignificant. CONCLUSION: Among these frail and very old patients with dementia, neither the use of atypical antipsychotics nor the use of conventional neuroleptics increased mortality or hospital admissions. The use of restraints, however, doubled the risk of mortality.     

Effectiveness of atypical antipsychotics for substance use in schizophrenia patients

OBJECTIVE: This study examined the influence of medication class (atypical antipsychotic, typical antipsychotic and no medication) and compliance on substance use outcomes for schizophrenia patients in the community. METHOD: N=362 adults with schizophrenia-spectrum disorder were followed for 3 years in a naturalistic study with structured interviews at 6-month intervals. Multivariable time-series analysis was performed using propensity-score adjustment for selection to medication class. RESULTS: Participants who were compliant with atypical antipsychotic medications for 90 days or more during each 6-month period were significantly less likely to use substances during the next 6-month period than patients who were compliant with typical antipsychotics or those who were not prescribed either type of medication for at least 90 days. CONCLUSION: Atypical antipsychotics may offer an advantage in reducing substance use among schizophrenia patients. For patients to benefit from atypical antipsychotics, treatment should focus on enhancing compliance and integrating substance use treatment.     

Typical and atypical antipsychotics in bipolar depression

BACKGROUND: Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression. DATA SOURCES: English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords antipsychotics, typical antipsychotics, atypical antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual antipsychotics were also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed. STUDY SELECTION: Use of a depression rating scale was required for inclusion of studies of the atypical antipsychotic agents in our analysis. DATA SYNTHESIS: Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical antipsychotics that support the conclusion that this class of medication worsens bipolar depression. CONCLUSION: Emerging data suggest that the atypical antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical antipsychotic agents worsen bipolar depression.     

Augmentation of antidepressants with atypical antipsychotics in non-delusional unipolar depressed patients with non-response to antidepressant-monotherapy

Objective Augmentation of antidepressants with atypical antipsychotics is used in depressive patients with non-response to antidepressants. We investigated the utility of this strategy.Methods Systematic computer-based search in the online library Pubmed for randomized placebo-controlled double-blind trials (RCT) from the years 1990 to 2011.Results We found 14 RCT about augmentation of antidepressants with atypical antipsychotics in depressive patients with non-response to antidepressants. Trials examined olanzapine, risperidone, quetiapine and aripiprazole.Conclusions Augmentation of antidepressants with atypical antipsychotics is an alternative to the augmentation with lithium in unipolar depressive patients with non-response to antidepressants. But treatment with atypical antipsychotics as opposed to placebo increases the risk of non-compliance due to side-effects of medication. Augmentation of antidepressants with atypical antipsychotics in unipolar depression is an off-label therapy in Germany except for the augmentation with extended-release quetiapine. Knowledge about treatment strategies regarding augmentation of antidepressants with atypical antipsychotics can increase the chance of a successful treatment, but interactions and side-effects should be considered.     

A randomized,placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia

The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population.     

Shuganjieyu capsule for major depressive disorder (MDD) in adults: a systematic review

Objectives: Shuganjieyu capsule is a pure herbal pharmaceutical product for depression. Our objective was to explore the effectiveness and safety of Shuganjieyu capsule for the treatment of major depressive disorder in adults.

Method: Eight computerized databases were searched. In addition, randomized controlled trials (RCTs) on Shuganjieyu capsule were hand-searched on seven key Chinese journals. Data were extracted and evaluated by two reviewers independently. Analysis was performed by intention-to-treat where possible. Prespecified subgroup analyses were different-dose regimens, patient spectrum, publication status, and treatment duration.

Results: Seven RCTs with 595 participants were included. Shuganjieyu capsule was superior than placebo in terms of response rate (RR = 2.42, 95% CI: 1.55–3.79; P = 0.0001), remission rate (RR = 4.29, 95% CI: 1.61–11.45; P = 0.004), the scores of the mean change from baseline of the HAM-D₁₇ (MD = ?4.17, 95% CI: ?5.61 to ?2.73; P < 0.00001) and from baseline of traditional Chinese medicine (TCM) syndrome score scale scores (MD = ?6.00, 95% CI: ?8.25 to ?3.75; P < 0.00001). In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate (RR = 1.56, 95% CI: 1.29–1.88; P < 0.00001) and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores (MD = ?0.74, 95% CI:?1.12 to ?0.35; P = 0.0002) than venlafaxine alone.

Conclusion: Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone. Due to the considerable risk of bias in majority of trials, recommendations for practice should be cautious, and additional, well-designed RCTs are needed in next step.     

Atypical antipsychotic medication improves aggression, but not self-injurious behaviour, in adults with intellectual disabilities

Objective Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self‐injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons. Method A retrospective review of 31 adult residents of a state developmental centre, who were treated for aggression and/or SIB with atypical antipsychotics. Average monthly counts of aggression and SIB for 1 year of treatment with typical antipsychotics, were compared with monthly averages for the next 12 months of treatment with atypical antipsychotics. Results Twenty‐seven of 31 subjects (87%) completed a full year of atypical antipsychotic treatment. Subjects ranged in age from 24 to 54 years (mean = 39); 18/31 (58%) had profound ID. Twelve of 26 (46%) had typical antipsychotics discontinued within the year of atypical treatment; another 7/26 (27%) had their typical antipsychotic dose decreased. Twenty‐three of 31 trials involved risperidone; 7/31 olanzapine; 1/31 quetiapine. Subjects gained an average of 6.6 pounds during the year of atypical treatment, but no significant changes in glucose or cholesterol were found. Subjects with aggression alone (N = 14) had significant decreases in the number of aggressive acts per month during the year of atypical treatment (P = 0.03); those with both aggression and self‐injury (N = 12), or those with self‐injury alone (N = 5) had no significant improvement. Conclusion The findings suggest that atypical antipsychotics can be successfully substituted for typical agents in individuals with ID and decrease the frequency of aggression over one year of treatment. The weight gain seen in our sample reinforces the necessity of regular monitoring of weight and metabolic changes in persons with ID treated with atypical antipsychotics.     

Antipsychotic treatment discontinuation in previously untreated patients with schizophrenia: 36-month results from the SOHO study

Data from the 3-year, prospective, observational SOHO study were used to compare the effectiveness (in terms of treatment discontinuation) and the tolerability of olanzapine, risperidone, other atypicals and typical antipsychotics in 1009 previously untreated outpatients with schizophrenia who started monotherapy at baseline. Kaplan-Meier survival analysis estimated the time to treatment discontinuation by the treatment group, Cox proportional hazards regression models identified the variables associated with treatment discontinuation (adjusted for baseline differences between treatment groups), and logistic regression models compared the tolerability profiles of the different treatment groups. Of the 931 patients analyzed, 31.9% discontinued the medication initiated at baseline during the 3-year follow-up. Olanzapine had the lowest rate of discontinuation (28.9%), followed by other atypical (34.0%), risperidone (36.2%) and typical antipsychotics (44.5%). Compared to olanzapine, risk of treatment discontinuation was higher with typical antipsychotics (hazard ratio [HR] 1.75; 95% confidence interval [CI] 1.11, 2.78) or risperidone (HR 1.36; 95% CI 1.02, 1.82). A higher baseline Clinical Global Impression (CGI) positive score was associated with a higher risk of treatment discontinuation (HR 1.18; 95% CI 1.06, 1.30). Olanzapine was associated with a lower frequency of extrapyramidal symptoms than other antipsychotics, fewer prolactin-related adverse events than risperidone and other atypical antipsychotics, but greater weight gain than typicals and risperidone. For all analyses, comparison with the other atypical group is limited due to its small sample size (n = 50). In conclusion, treatment effectiveness and tolerability varied among antipsychotic medications in previously untreated patients with schizophrenia. The results should be interpreted conservatively given the observational study design.     

Discontinuing antiepileptic drugs in children with epilepsy: A prospective study

In a prospective study, antiepileptic drugs were discontinued in 264 children with epilepsy after a mean seizure-free interval of 2.9 years. They were then followed for a mean of 58 months to ascertain whether seizures recurred. Seizures recurred in 95 (36%) of the children. Etiology was a significant predictor of outcome (relative risk [RR] = 1.81). On multivariable analysis, significant factors in the idiopathic group included age at onset above 12 years (RR = 5.4), a family history of seizures (RR = 3.1), the presence of slowing on the electroencephalogram prior to medication withdrawal (RR = 2.4), and a history of atypical febrile seizures (RR = 2.8). Specific epileptic syndromes such as juvenile myoclonic epilepsy and benign rolandic epilepsy were also significant predictors of outcome. In the remote symptomatic group, significant predictors of outcome included age at onset older than 12 years (RR = 3.6), moderate to severe mental retardation (IQ < 50) (RR = 2.8), a history of atypical febrile seizures (RR = 2.0), and a history of absence seizures (RR = 0.4). The majority of children with epilepsy in remission while on antiepileptic drug therapy will remain seizure free when medications are withdrawn. A few readily available parameters distinguish those with a good prognosis from those in whom seizures are likely to recur. These data provide the framework for the clinical decision making for withdrawal of medications in these children.