Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.

BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.     

Update and recommendations for the use of antipsychotics in early-onset psychoses.

A review was undertaken of studies evaluating the efficacy and tolerability of antipsychotic medications for the management of psychosis in children and adolescents. All identified published and unpublished studies from 1996 onward were included for review. The search located one randomized control trial, seven open-label trials, six retrospective chart reviews, and nine case reports. The studies assessed the use of haloperidol, clozapine, risperidone, olanzapine, and quetiapine in the management of psychosis in children and adolescents. Most studies reported reasonable treatment response; however, extrapyramidal side effects, sedation, and weight gain are concerning. This points to the need for appropriate baseline assessments prior to initiating treatment with these agents. Particular attention should be given to assessment of the extrapyramidal system as well as to baseline weight, lipid profile, and blood glucose. Further study is needed to refine the use of antipsychotic medications in children and adolescents in order to minimize adverse effects while conferring an optimum therapeutic response. The importance of instituting effective early treatment in youth with psychoses is an important goal that may serve to lessen the long-term morbidity of the illness.     

Dopamine and incentive learning: A framework for considering antipsychotic medication effects

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.     

Control group bias in randomized atypical antipsychotic medication trials for schizophrenia

CONTEXT: It has been suggested that the need for concurrent placebo control groups in new schizophrenia studies might be minimized by making comparisons with external placebo. This strategy requires an assumption of constancy, that the novel medication will perform the same way in a study with only active controls as it would have in a placebo-controlled trial. OBJECTIVE: To test this constancy assumption in active- and low dose-controlled trials vs placebo-controlled trials of atypical antipsychotic medications. DATA SOURCES: A comprehensive search of bibliographic databases, conference proceedings, and Food and Drug Administration databases through November 24, 2003. STUDY SELECTION: English-language, randomized, double-blind clinical trials of newer atypical antipsychotic medications in otherwise unselected acutely ill adults with schizophrenia or schizoaffective disorder that reported baseline and intent-to-treat end point change values for the Brief Psychiatric Rating Scale. DATA EXTRACTION: Study number, sample size, reported dosage for each arm, trial duration, percentage of men, average age, trial arm treatment completion rate, baseline and within-arm end point change in the Brief Psychiatric Rating Scale, method of scoring the Brief Psychiatric Rating Scale, and date of publication were extracted from each study independently by 2 of us (S.W.W. and C.B.B.) each. DATA SYNTHESIS: There were 32 studies comprising 66 risperidone, olanzapine, quetiapine, and ziprasidone arms including 7264 patients. Random-effects analysis revealed that in atypical antipsychotic medication arms, the degree of improvement was nearly double in active-controlled trials than that seen with the same drugs and dosages in placebo-controlled studies. An effect of design was also observed in low dose-controlled studies vs placebo-controlled studies in ineffective and intermediate antipsychotic medication dose ranges. CONCLUSIONS: The observed control group bias indicates that the constancy assumption does not hold in recent antipsychotic medication trials. These results suggest that caution is indicated when considering active- or low dose-controlled studies requiring comparisons with external placebo as alternatives to placebo-controlled trials for establishing efficacy of new medications for schizophrenia.     

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.     

Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods.

BACKGROUND: We performed a retrospective analysis of data involving 121 inpatients to examine the rate of weight gain during antipsychotic-free periods and during treatment with various antipsychotic drugs. METHOD: Data were analyzed to determine differences in weekly weight change during antipsychotic-free (N = 65), typical antipsychotic (N = 51), or atypical antipsychotic (N = 130) treatment periods. Atypical antipsychotic treatment periods were further subdivided into olanzapine (N = 45), clozapine (N = 47), or risperidone (N = 36) treatment periods. A paired comparison was conducted on 65 patients who had an antipsychotic-free treatment period preceding or following a neuroleptic drug treatment period. In addition, patients were classified as either non-obese (with a body mass index [BMI] < or = 29.9 kg/ml) or obese (BMI > or = 30.0 kg/m2) to test whether the rate of weight gain during treatment periods was related to initial BMI. RESULTS: Across all treatment periods, weekly weight gain was as follows: 0.89 lb/wk (0.40 kg/wk) on atypical antipsychotic medication, 0.61 lb/wk (0.27 kg/wk) on typical antipsychotic medication, and 0.21 lb/wk (0.09 kg/wk) on no antipsychotic medications. The atypical antipsychotic versus antipsychotic-free comparison was significant (F = 3.51; df = 2,231; p = .031), while the typical antipsychotic versus antipsychotic-free comparison was not. Among the individual atypical antipsychotic medications, significantly more weight gain occurred during olanzapine treatment (1.70 lb/wk) (0.76 kg/wk) than with either clozapine (0.50 lb/wk) (0.22 kg/wk) or risperidone (0.34 lb/wk) (0.15 kg/wk) treatments (F = 7.77; df = 2,117; p = .001). In the paired analysis with patients serving as their own controls, the difference between weekly weight gain during atypical antipsychotic treatment and antipsychotic-free treatment was significant (t = -3.91; df = 44; p = .001), while the difference between weight gain during typical antipsychotic treatment and antipsychotic-free treatment was not significant. With the individual drugs. treatment with both olanzapine and clozapine caused significantly higher weekly weight gain than antipsychotic-free treatment (p = .001 and p = .036, respectively). while treatment with risperidone did not. Non-obese patients (BMI < 29.9 kg/m2) and obese patients (BMI > 30.0 kg/m2) did not differ significantly in their weight gain during typical or atypical antipsychotic treatment. CONCLUSION: Treatment with atypical antipsychotics was associated with more weight gain than treatment with typical antipsychotics. Among the atypical drugs, olanzapine was associated with more weight gain than either clozapine or risperidone. The patient's admission BMI was not associated with the amount of weight gained during subsequent antipsychotic treatment.     

Medication adherence for children and adolescents with first-episode psychosis following hospitalization

The objective of this study was to examine the predictors associated with adherence to atypical antipsychotic medication following discharge from hospital for children and adolescents with first-episode psychosis. Sixty-five children and adolescents, age 15.35 ± 2.08 years, 59% boys, who had participated in a longitudinal cohort study examining relapse following first hospitalization for episode of psychosis were included in this study. All those studied were discharged on one of three atypical antipsychotics, risperidone, quetiapine, or olanzapine between January 1999 and October 2003. Time 1 data were collected retrospectively from medical charts using a standardized questionnaire; time 2 data were obtained using questionnaire mailed to participants’ parents a minimum of 2 years post-discharge, mean 3.9 ± 1.3 years. Variables examined as predictors of adherence fell into broad categories of biological, social and treatment variables. Discharge on concurrent pharmacologic agent for affective symptoms in addition to atypical antipsychotic, OR = 10.5 [95% confidence interval (CI) = 2.06–53.19] was a strong predictor of medication adherence in adolescents. The results indicated that children and adolescents discharged from their first hospitalization following a psychotic episode may be more likely to stay on prescribed antipsychotic medication if they are prescribed concurrent medication for affective symptoms.     

Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease.

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS     

Psychotropic medication for behaviour problems in people with intellectual disability: a review of the current literature

PURPOSE OF REVIEW: A high proportion of people with intellectual disability have behaviour problems and psychotropic medication is a commonly used management strategy for these behaviours, despite lack of good-quality evidence to support this practice. RECENT FINDINGS: In recent years, one randomized controlled trial among adults and four on children with intellectual disability have been published showing effectiveness of low-dose risperidone in the management of behaviour problems as compared with placebo. Most of these randomized controlled trials are of good quality and included a reasonable number of participants. Most of these studies showed adverse effects, however, somnolence and weight gain particularly being associated with risperidone treatment. Most of the evidence on other psychotropic medications such as antidepressants, mood stabilizers, antianxiety drugs and opioid antagonists is difficult to interpret because it is based primarily on small case studies. SUMMARY: There is growing evidence in support of some antipsychotic medication, particularly the atypical antipsychotic, risperidone. Many of the studies of effectiveness included in this review have methodological flaws however. Therefore, the results need to be interpreted with caution. Furthermore, the paucity of evidence for some groups of medication does not necessarily mean that these medications are ineffective, but rather that their use is not currently supported by good-quality research.     

Pharmacotherapy of irritability in pervasive developmental disorders

Children and adolescents diagnosed with autism and related pervasive developmental disorders (PDDs) often sustain irritability, including aggression, self-injurious behavior, and tantrums. Research to date supports the use of the atypical antipsychotics as a first-line pharmacologic treatment for this target symptom domain in PDDs. Currently, the atypical antipsychotic risperidone is the only medication approved by the US Food and Drug Administration for irritability in youth with autism. Additional large-scale, placebo-controlled studies of other medications are needed to determine their efficacy for the treatment of irritability in this diagnostic group.     

Risperidone in the treatment of bipolar mania

Atypical antipsychotic medications have assumed growing importance for the treatment of bipolar disorder, an illness that affects approximately 1.2%–3.7% of the general population in a given year. Current practice guidelines for the treatment of bipolar mania support the use of atypical antipsychotic medications as monotherapy or as a component of polytherapy, and in clinical settings the use of atypical antipsychotics to treat bipolar disorder is widespread. Risperidone is an atypical antipsychotic, sometimes referred to as a second-generation antipsychotic. The receptor-binding profile of risperidone, which includes potent antagonism of the serotonin 5-HT2_A, dopamine D₂, and alpha-adrenergic receptors, is believed to be related to positive effects on mood. The FDA-approved bipolar indications for risperidone include: 1) monotherapy for short-term treatment of acute manic or mixed episodes associated with bipolar I disorder and 2) combination therapy with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder. This review of risperidone for bipolar mania will address the chemistry, pharmacodynamics, pharmacokinetics, and metabolism of risperidone, use with concomitant medications, clinical trials in bipolar mania, as well as safety and tolerability issues. Finally, dosing and administration are addressed as well as use for bipolar mania in geriatric, child, or adolescent patients.     

Effectiveness of atypical antipsychotic medications in reducing violent behavior among persons with schizophrenia in community-based treatment

This study prospectively compared the effectiveness of atypical antipsychotic medications to that of conventional neuroleptics in reducing violent behavior among patients with schizophrenia under "usual care" conditions in the community. Participants (n = 229) were adults with schizophrenia spectrum disorders receiving inpatient or outpatient services in public sector mental health systems in North Carolina. Subjects were followed for 2 years in an observational study using multiple methods of data collection at 6-month intervals to assess treatment, sociodemographic characteristics, clinical features, and violence outcomes. Treatment with atypical antipsychotic medications (clozapine, risperidone, or olanzapine) was found to significantly reduce the risk of violent behavior, whereas treatment with conventional neuroleptics did not have this same beneficial effect. A cumulative effect on reduced violence was attributable to consistent compliance with atypical antipsychotic medications over a 2-year period. Concurrent reductions in psychotic symptoms, substance abuse, and adverse medication side effects were found to mediate the association between adherence with atypicals and lower violence risk. Treatment with atypical antipsychotic medications should be considered as an important component of violence risk management for schizophrenia patients at risk for violent behavior.     

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.     

Managing treatment-resistant schizophrenia: evidence from randomized clinical trials

Clozapine was the first antipsychotic medication to be approved for the indication of treatment-refractory schizophrenia. This followed rigorous testing in patients who retrospectively and prospectively failed treatment trials of relatively high doses of conventional antipsychotics. In the past decade, other atypical antipsychotics have been approved, but they have not been designated specifically for patients with a history of prior poor treatment response. Better tolerated than clozapine, these new agents have been used with varying success in patients who would have otherwise received clozapine. Up until very recently there has not been a head-to-head controlled clinical trial comparing the two most commonly used atypical antipsychotics, risperidone and olanzapine, with clozapine in patients considered to have a suboptimal response to typical antipsychotics. This review summarizes the current advances made in the pharmacological management of these patients by examining recently published randomized controlled clinical trials that have measured psychopathology and cognition.     

The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive developmental disorders

Research into the pharmacotherapy of autistic disorder has steadily increased over the past two decades. Several psychoactive medications have shown efficacy for selected symptoms of autistic disorder and can be used to augment critical educational and behavioral interventions that are the mainstays of treatment. A comprehensive review of medication trials conducted in individuals with autistic disorder and other pervasive developmental disorders is presented. The typical antipsychotic haloperidol is the best-studied medication in autistic disorder but is associated with a high rate of dyskinesias. Investigations to date suggest that the atypical antipsychotics such as risperidone have efficacy for certain symptoms of autistic disorder and may be better tolerated than typical antipsychotics. Preliminary results from trials with serotonin-reuptake inhibitors are favorable, although efficacy has not been demonstrated in younger age groups. Recent controlled studies of nalfrexone suggest that the drug has minimal efficacy. In two small controlled investigations, clonidine was more effective than placebo for a variety of symptoms, including hyperactivity and irritability; in one of these studies, however, the majority of patients relapsed within several months. Psychostimulants reduced hyperactivity and irritability in one small double-blind crossover study in children with autistic disorder, although these agents are frequently reported to exacerbate irritability, insomnia, and aggression in clinical populations. Recent controlled trials of secretin have not shown efficacy compared to placebo. Several other medications, including buspirone, mood stabilizers, and beta-blockers, have produced symptom reduction in some open-label studies and may warrant controlled investigation.     

Efficacy of atypical antipsychotic medication in the management of behaviour problems in children with intellectual disabilities and borderline intelligence: a systematic review

The use of medications to manage problem behaviours is widespread. However, robust evidence to support their use seems to be lacking. The aim was to review research evidence into the efficacy of atypical antipsychotic medication in managing problem behaviour in children with intellectual disabilities and borderline intelligence. A systematic review was conducted for placebo-controlled randomised double-blind trials. The included studies (N = 6) showed that risperidone was significantly more effective than placebo in managing problem behaviours. However, most studies highlighted adverse events primarily somnolence and weight gain. There is now some evidence in favour of the use of risperidone. However, because of possible adverse events, these medications have to be used with caution.     

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: A longitudinal MRI study

BackgroundPituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations.AimsTo determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population.MethodPituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3 months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication.ResultsThere was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r = ? 0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses.ConclusionsAtypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.     

Psychosis and antipsychotic medications in Alzheimer's disease: clinical management and research perspectives

Psychosis is common in patients with Alzheimer's disease (AD) and contributes substantially to patient morbidity and caregiver distress. Antipsychotic medications are used to treat psychosis and other psychiatric or behavioral symptoms in AD, although optimal treatment guidelines have been elusive. Choosing the most advantageous medication for an individual patient is challenging. This article provides an overview of clinical management principles and medication treatment strategies for patients with AD and psychosis. Effects of individual medications are also described. Medications in the conventional neuroleptic, atypical antipsychotic, cholinesterase inhibitor, and serotonergic classes have been shown to ameliorate psychosis and behavioral symptoms in patients with AD, although the evidence is not conclusive for many medications. Side effects vary substantially across medication classes and modestly among individual patients. Improvement in agitation, aggression, or other behaviors with antipsychotic medication treatment may not depend on distinct antipsychotic effects. In contrast, there is preliminary evidence that delusions and hallucinations may respond to treatment with medications outside the antipsychotic class. Many important clinical questions warrant further research study. In particular, studies to compare how individual symptoms respond to different medications, and to examine how to best manage overlapping symptoms or incomplete treatment response are needed.     

Augmentation with amisulpride for schizophrenic patients nonresponsive to antipsychotic monotherapy

Despite the effectiveness of antipsychotic medications in treatment of schizophrenia, about 30% of patients who receive an adequate treatment have significant persisting symptoms. The problem of treatment-resistant psychosis is an important and difficult one. The aim of this study was to retrospectively evaluate the efficacy and safety of amisulpride augmentation in treatment-resistant schizophrenic patients. To the best of our knowledge, this is the first report about resistant schizophrenic and schizoaffective patients treated with the combinations of risperidone and amisulpride and ziprasidone and amisulpride. Data were collected from patient records. A total of 15 resistant schizophrenic patients (7 men, 8 women, 54.0 +/- 16.9 years old) were included in the study. Before addition of amisulpride, the patients were treated with monotherapy by atypical neuroleptics (clozapine, olanzapine, risperidone, or ziprasidone). The mean amisulpride dose was 693.3 +/- 279.6 mg/d. The mental state of 12 (80%) patients treated with combination was improved. Three (20%) patients showed no change in their mental state. Only 2 patients treated with a combination of risperidone and amisulpride had mild side effects. The results are preliminary and require confirmation in a randomized controlled trial. The authors suggest that amisulpride may be a promising option as an augmentation strategy in treatment-resistant schizophrenic patients.