[Clinical and socio-demographic profile of patients with schizophrenia according to the antipsychotic treatment prescribed]. / Analyse du profil socio-démographique et clinique de patients schizophrènes en fonction du traitement neuroleptique reçu.

INTRODUCTION: Data concerning the characteristics of patients with schizophrenia and their treatment in day hospitals are scarce. Guidelines for clinical practice are, however, regularly published. Recommendations from the 1994 Consensus Conference underline the necessity of antipsychotic monotherapy in the long term treatment of schizophrenia. In the US the Schizophrenia Patient Outcome Research Team (PORT) published in 1999 treatment recommendations concerning the use of antipsychotics in the acute phase and in maintenance. For maintenance, the recommended dose should be between 300 and 600 mg/day (CPZ equivalents) (recommendation n 4). AIM OF THE STUDY: The aim of this study is to establish the socio-demographic and clinical profile of patients according to the dose of antipsychotic medication prescribed. The study also examines the use of antipsychotic polypharmacy. DESIGN: of the study. For this study, 116 patients treated in 12 different day hospital units were recruited. Inclusion criteria were: a DSM IV diagnosis of schizophrenia, being treated in a day hospital and having received antipsychotic medication for at last 2 months. Instruments were the MINI for a standardized diagnosis of schizophrenia, the CGI and the PANSS. Prescribed doses were transformed in chlorpromazine (CPZ) equivalents, in order to establish comparisons between patients. RESULTS: The population sample was composed of 72 male (61.5%) and 44 female (38.5%) patients. The mean age was 36.4 years old. The mean education level was 11.3 years. A large majority (n=103, 88%) of patients was celibate, 65 patients (55.6%) lived on their own, the others lived with their family (45 patients, 38.5%) or with a spouse (7 patients, 6%). A large majority of patients (75.6%) received some form of state allowance. Only 1.7% were receiving a salary. The mean antipsychotic dose was 660 mg/day and 68% of patients were treated with an atypical antipsychotic (amisulpride, clozapine, olanzapine, risperidone). Thirty-two percent of patients were treated with doses between 600 and 1,000 mg/day and 24% with doses above 1,000 mg/day. When comparing patients according to the dose level they were receiving (<300 mg/day; 300 to 599 mg/day; and 600 to 999 mg/day;>1,000 mg/day), there was no significant difference between groups for socio-demographic variables. Patients treated with doses below 300 mg/day had a better psychosocial profile and were more often treated with loxapine, haloperidol and risperidone. Patients treated with doses above 1,000 mg/day were more often receiving clozapine. There was still a substantial number of patients treated with conventional antipsychotics in the above 1,000 mg/day range. Patients receiving an antipsychotic monotherapy were more often treated with clozapine or olanzapine and presented a higher rate of positive symptoms. DISCUSSION: These results are discussed in comparison with present guidelines concerning the treatment of patients with schizophrenia.

[Antipsychotics in bipolar disorders]. / Antipsychotiques et troubles bipolaires.

This article is a review of the various treatments that are currently available, in particular in France, for the treatment of bipolar disorders. This article specifically addresses the use of novel antipsychotic agents as alternative therapy to a lithium therapy and/or the use of conventional antipsychotics. The prevalence of bipolar disorder over a lifetime is around 1% of the general population. Bipolar disorder consists of alternating depressive and manic episodes. It mainly affects younger subjects, and is often associated with alcohol and drug addictions. There are two main subtypes of bipolar disorder. According to the DSM IV-R, type 1 of bipolar disorder is characterised when at least one manic episode (or a mixed episode) has been diagnosed. Type 2 of bipolar disorder is related to patients enduring recurrent depressive episodes but no manic episode. Type 2 affects women more frequently as opposed to type 1 affecting individuals of both sexes. Manic-depressive disorder (or cyclo-thymic disorder) appears in relation to patients who has never suffered manic episode, mixed episode or severe depressive episode but have undergone numerous periods with some symptoms of depression and hypomanic symptoms over a two-year period during which any asymptomatic periods last no longer than two months. The average age of the person going through a first episode (often a depressive one) is 20 years-old. Untreated bipolar patients may endure more than ten manic or depressive episodes. Finally, in relation to 10 to 20% of patients, the bipolar disorder will turn into a fast cycle form, either spontaneously or as a result of certain medical treatments. Psychiatrists are now able to initiate various treating strategies which are most likely to be effective as a result of the identification of clinical subtypes of the bipolar disorder. Lithium therapy has been effectively and acutely used for patients with pure or elated mania and its prophylaxis. However, lithium medication may worsen depressive symptoms when used for a long term maintenance therapy. Additionally, mixed mania, rapid cycling type patients and bipolar disorder associated with substance abuse do not respond well to lithium therapy. In addition to the lithium therapy or in place of a lithium therapy, one can report the frequent use of antipsychotic agents in respect of patients with bipolar disorder during both the acute and maintenance phases of treatment. Antipsychotic agents have been used for almost forty years and may be used in combination with a lithium therapy. Conventional antipsychotics are effective but they may induce late dyskinesia, weight gain, sedation, sexual dysfunction and depression. These adverse side effects often lead to non compliance in particular in circumstances where antipsychotic agents are combined with a lithium therapy. A number of alternative somatic treatment approaches have been reported for patients who do not respond well or who are intolerant to lithium therapy. As such, valproate has received regulatory approval for the acute treatment of mania and carbamazepine has been indicated for this condition in a number of countries. Divalproex (Depakote) has recently obtained the authorization to market in France and may be prescribed for manic states or hypomanic states that do not tolerate lithium therapy or for which lithium therapy is contraindicated. A number of other anticonvulsants (lamotrigine, gabapentin and topiramate) are currently being tested. Because of the side effects of the conventional antipsychotic agents, atypical antipsychotic agents are currently on trial and appear to be of interest in the treatment of bipolar disorders. Currently, a number of prospective studies are available with clozapine, risperidone and olanzapine in the treatment of bipolar disorder. Most are short-term studies. Recent randomised, double-blind, placebo-controlled studies have shown clozapine, risperidone and olanzapine to be effective with antimanic and antidepressive effects, both as monotherapy and as add-on maintenance therapy with lithium or valproate. They also have a favorable side effect profile and a positive effect on overall functioning. Similarly, valproate combined with antipsychotics provides greater improvement in mania than antipsychotic medication alone and results in lower dosage of the antipsychotic medication. There is currently no double-blind study regarding the use of clozapine for bipolar disorders. However, based on the results of a number of open-label studies, clozapine appears to be effective in relation to schizo-affective and bipolar patients including those with rapid cycling or those who respond inadequately to mood stabilizers, carbamazepine, valproate or conventional antipsychotics. Clozapine seems to be more appropriate for bipolar and schizo-affective patients than schizophrenics. In particular, studies show that patients with manic and mixed-psychotic state of illness are better responders than patients with major depressive syndromes. Four open studies suggest the efficacy of clozapine in the maintenance treatment of bipolar disorder and three prospective, open-label studies show the efficacy of clozapine in the manic state of the illness. However, the number of patients in the studies was not important and these studies are not controlled. Clozapine has also adverse side affects, one of which consisting of a major risk of agranulocytosis and, potentially, death. In addition, clozapine has been shown to produce significant weight gain and sialorrhea as well as significant anticholinergic effects. As a result, clozapine should not be prescribed in the first place. As opposed to clozapine, there are open-label reports and controlled studies in respect of risperidone and olanzapine. Two recent double-blind studies of acute mania found olanzapine to be more effective than placebo. Based on these two studies, olanzapine has recently been approved for the indication of mania. The effects of olanzapine and divalproex in the treatment of mania have also been compared in a large randomized clinical trial. The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission. Significantly more weight gain and cases of dry mouth, increased appetite and somnolence were reported with olanzapine while more cases of nausea were reported with divalproex. The comparison of olanzapine with lithium for the treatment of mania has also been the subject of a double-blind randomized controlled trial. That study shows no differences between the two drugs. While these studies support the idea that olanzapine has direct acute anti-manic effects, a number of authors are of the opinion that olanzapine may have specific prophylactic mood-stabilizing properties. Olanzapine would appear to be effective in the maintenance treatment, as it exhibited both antimanic and antidepressant effects. Systematic trials have shown that risperidone may be effective and safe in the treatment of acute mania, as an add-on therapy with lithium or valproate (open studies and two controlled double-blind studies) and as monotherapy (open studies). In an open, multi-center, 6-month study, risperidone seems to be effective and safe as long-term adjunctive therapy in treatment-resistant bipolar and schizo-affective disorders, with no exacerbation of manic symptoms. Risperidone had few adverse side effects (and where there were any, they were mostly mild), mostly consisting of APS and weight gain. A naturalistic comparison of clozapine, risperidone and olanzapine in the treatment of bipolar disorder suggests that the efficacy and tolerability of the three treatments are similar. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. However, this may partially be caused by the use of mood-stabilizing agents. Bipolar and schizo-affective patients now require combination therapy approach because of the cyclic nature of these disorders. Many studies report the combination of mood-stabilizing agents with conventional antipsychotics and atypical antipsychotics. Combination therapies produce a number of adverse side effects. Atypical antipsychotics (other than clozapine) are now rated as first-line agents for adjunctive treatment of mania because they produce less adverse side effects. Atypical antipsychotics are also rated as first-line agents for combined treatment of psychotic depression and they are strongly preferred when an antipsychotic is required for long-term maintenance.