Adjunctive antipsychotic treatment is necessary for adolescents with psychotic mania

Adolescents with acute psychotic mania were treated with lithium and adjunctive haloperidol as part of a lithium efficacy study. If the psychosis completely resolved, haloperidol was discontinued after 1 week of therapeutic lithium levels. Our first five subjects experienced a rapid exacerbation of symptoms, which responded to restarting haloperidol. A longer duration of adjunctive antipsychotic treatment is necessary in adolescents with bipolar psychosis.     

Lithium treatment of acute mania in adolescents: a large open trial

OBJECTIVE: To examine initial response to treatment in a large sample of acutely manic bipolar I adolescents and to examine potential predictors of nonresponse, such as the presence of prominent depressive features, psychosis, or psychiatric comorbidity. METHOD: Adolescents, 12 to 18 years of age, with an acute manic episode were treated with open lithium. Response was defined as a decline in Young Mania Rating Scale total score of >or=33% and a rating of "much improved" or "very much improved" on the Clinical Global Impressions Improvement item at week 4. Remission of mania was defined as a Young Mania Rating Scale score of 相似文献   

Mood-incongruent versus mood-congruent psychosis: differential antipsychotic response to lithium therapy

The authors previously reported that a subgroup of schizophrenic-like patients respond favorably to lithium (Li) therapy, as do patients with a classical manic illness. In the present study, the time course of psychotic and affective symptom remission after Li therapy was examined in these two groups of patients. Li responsive patients with a mood-incongruent psychosis (schizophrenic-like illness) demonstrated a rapid antipsychotic response to Li therapy, showing a 50% improvement during the first 7 days, while no improvement in affective symptoms was seen until week 2 or 3 of treatment. Alternatively, patients with a mood-congruent psychosis (where mania is the primary diagnosis) demonstrated no antipsychotic response to Li therapy during the first 2 weeks of treatment, while some improvement in manic symptoms occurred during treatment week 2. The present study demonstrates that Li therapy differentially affects psychotic symptoms in mood-incongruent as opposed to mood-congruent psychosis. Further, the growth hormone (GH) response to apomorphine administration differentiated these two groups of Li responsive patients. Patients with a Li responsive mood-incongruent psychosis demonstrated over a seven-fold greater GH response than mood-congruent psychotic patients. The present data suggest that mood-incongruent and mood-congruent psychoses may represent two biologically distinct psychotic processes separable by both medication response and central dopamine function.     

Psychosis in mania: specificity of its role in severity and treatment response

BACKGROUND: Psychosis is a prominent characteristic of manic episodes. We investigated relationships between the presence of psychotic features, the severity of the manic syndrome, and syndrome severity's response to treatment. METHOD: 179 subjects meeting Research Diagnostic Criteria for a manic episode of bipolar I disorder were hospitalized for acute manic episodes and treated in a randomized trial of lithium, divalproex sodium, or placebo. Factor and cluster analyses were carried out using the clinician-rated Schedule for Affective Disorders and Schizophrenia, Change version (SADS-C) and the nurse-rated Affective Disorder Rating Scale (ADRS). RESULTS: Subjects with psychotic features had significantly (p < .005) greater overall impairment (lower Global Assessment Scale [GAS] scores) but did not differ in severity of mania scores compared with those without psychotic features. Psychosis factor scores correlated significantly (p < .000001) with GAS scores but not with mania scores. Baseline psychosis factor scores did not correlate with subsequent treatment-associated change in mania scores, but change in mania scores during treatment correlated significantly (p < .000001) with change in the psychosis factor. Changes in psychosis factor scores correlated significantly with changes in mania rating scale scores regardless of treatment. CONCLUSIONS: Psychotic features as a component of manic episodes contribute substantially to overall impairment. Treatments that successfully treat mania also reduce psychosis scores.     

Gabapentin in geriatric mania

There is little available information on anticonvulsant treatment of mania in elderly patients. Seven elderly patients, each in a manic episode, were treated with gabapentin. All 7 patients experienced improvement in manic symptoms, with minimal to no side effects. They received gabapentin in combination with antipsychotic medications, and in 1 case in combination with valproate. Gabapentin appears to be a safe and effective treatment in geriatric mania when combined with antipsychotic medications or valproate. Gabapentin appears to be well tolerated with no major adverse drug interactions or side effects in elderly manic patients. This case series suggests that controlled studies are warranted to examine gabapentin's efficacy and side effects, particularly as an adjunctive medication, in geriatric mania.     

Adjunct treatments in acute mania

When treating patients with manic states, the physician has to deal with at least two main Issues. First, the therapeutic decision has to be rapid because of the unpredictability of its immediate course. This concerns often results in polypharmacy with adjunct treatments. However, the therapeutic choice has to be cautious since part of the treatment will be maintained for prophylaxis. According to recent guidelines, the use of monotherapy with mood stabilisers during acute manic states concerns only few patients with mostly hypomania to moderate mania. Up to date, antipsychotics and benzodiazepines are considered as adjunct treatment in mania with psychotic symptoms or hostility. However, survey studies show that antipsychotics are widely used as adjunct treatments to mood stabilisers, indeed beyond the indications held by the guidelines. Our objective was to describe the clinical situations justifying the addition of an adjunct treatment during acute mania and to clear up from published data, the advantages and the inconveniences of combining antipsychotics and/or benzodiazepines with a mood stabilisers in order to define differentiated indications. Mania associated with either agitation, sleep disturbances or psychotic symptoms requires most of the time to combine mood stabiliser and respectively, sedative and/or anxiolytic, hypnotic or anti-psychotic treatments. Patients suffering from mania associated with other disorders need specific treatment adjustment and combination related to their medical condition. Adjunctive conventional antipsychotic remains widely used in first intention treatment. The conventional antipsychotic is often prescribed alone in the first weeks prior to the association with a mood stabiliser. Nevertheless there are controversies in the literature about their efficiency and their delay of action with regard to other treatments. When the conventional antipsychotic is a part of their initial treatment, manic patients remain taking them when discharged from hospital and are still taking them after 6 Months in a great percentage of the cases. The adverse events with conventional antipsychotic are numerous and severe enough in bipolar patients to restrict their use in first intention mainly to psychotic mania. Moreover, there are evidences for higher sensitivity to adverse effects of the conventional antipsychotics in manic patients. When agitation in acute mania requires an adjunct to mood stabiliser, the conventional antipsychotic treatment could be use for over-excitation without catatonic features and with particular care with the risk of akathisia. Long term effects of conventional antipsychotics, especially on depressive recurrences, should argue to stop them as soon as possible. Since the safety of adjunctive new antipsychotics with mood stabilisers seems until now acceptable, its indication should be limited to acute psychotic manias. Adjunctive benzodiazepine, should be evaluated in the various types of mania with specific concerns with comorbidity frequently met in consultation-liaison psychiatry. Benzodiazepines plus mood stabilisers may be the treatment of choice for the manias in which anxious state, catatonic symptoms or sleeplessness.     

Sertraline and Psychotic Symptoms: A Case Series

Sertraline and other SSRIs have a relatively favorable side-effect profile and are widely prescribed. We report the emergence of psychotic symptoms during treatment with sertraline in four patients. Three of these patients had a history of psychotic illness and were on antipsychotic medication, when sertraline was added. The psychotic symptoms emerged within 3 days–7 weeks of starting sertraline and resolved on its discontinuation. We wish to alert clinicians to the possibility that sertraline may provoke or exacerbate positive psychotic symptoms, particularly in patients on neuroleptics, with a previous history of psychosis.     

Atypical antipsychotics: efficacy across bipolar disorder subpopulations

Atypical antipsychotic medications, used as monotherapy or as adjunctive therapy with mood stabilizers, have shown efficacy and tolerability for 4 subpopulations of patients with bipolar disorder: patients with mixed mania, patients with psychotic episodes, children and adolescents, and the elderly. Patients experiencing mixed mania generally respond poorly to lithium therapy and are more difficult to treat than patients with pure mania. Atypical antipsychotics are increasingly being considered for this bipolar subpopulation because of their efficacy as antimanic agents, and because they are less likely to cause as many or as severe adverse events as conventional antipsychotics. Atypical antipsychotics have also demonstrated beneficial effects as monotherapy and adjunctive therapy for bipolar I disorder patients experiencing psychotic states. In addition, they have shown effectiveness and tolerability in small-scale and open-label trials and case studies with pediatric and geriatric bipolar patients.     

Antipsychotic drug treatment in first-episode mania: a 6-month longitudinal study

OBJECTIVE: To determine the use of antipsychotics during and following inpatient treatment of patients with a first-episode of mania. METHOD: The 198 subjects available for analysis were 129 consecutively hospitalized first-episode manic patients and 69 nonaffective psychotic patients assessed at admission and at 6-month follow-up postdischarge. Comparisons between the groups were made on frequency, type, and doses of antipsychotics prescribed during and after hospitalization in relation to clinical status. RESULTS: First-episode manic patients were given lower mean +/- SD daily doses of antipsychotics than nonaffective psychotic patients at discharge (163 +/- 132 mg chlorpromazine equivalents [CPZe] vs. 224 +/- 167 mg CPZe, p = .0102), at 6-month follow-up (109 +/- 167 mg CPZe vs. 260 +/- 178 mg CPZe; p = .0001), and if recovered (110 +/- 174 mg CPZe vs. 265 +/- 207 mg CPZe, p = .0014). At 6-month follow-up, 31 (24%) of 129 manic and 24 (35%) of 69 nonaffective psychotic patients continued to receive antipsychotics (NS). There was no difference between the groups in the time to discontinuation of antipsychotic agents. The mean time to drug discontinuation in manic patients was 98 days. CONCLUSION: (1) Antipsychotic doses at discharge and at 6-month follow-up were much lower in manic than in nonaffective psychotic patients, although there was no significant difference in the proportion of patients who continued to receive them 6 months after discharge. (2) The time to discontinuation was independent of clinical outcome. In those who discontinued the antipsychotic agent, the time to discontinuation was more rapid in the manic group than in the nonaffective psychotic patients.     

Evidence Base for Using Atypical Antipsychotics for Psychosis in Adolescents

Atypical antipsychotic medications have been the first line of treatment for adolescents with psychosis in the past couple of decades. Till the late 90s, there were very few randomized controlled trials (RCTs) on the treatment of adolescents with psychosis, although a fifth of schizophrenia starts during adolescence. Most of the treatment guidelines for adolescents with psychosis were derived from data on adults. In the past 10 years, there has been increasing number of studies on adolescents with psychosis. The current paper summarizes the findings of trials on adolescents with psychosis in 4 groups: (a) atypical antipsychotic medications vs placebo, (b) atypical antipsychotic medication vs typical antipsychotic medications, (c) one atypical antipsychotic medication vs another atypical antipsychotic medication, and (d) Low dose vs standard dose of atypical antipsychotic medication. We included 13 RCTs, with a total of 1112 participants. Although our review suggest that atypical antipsychotic medications are as effective as typical antipsychotic medications as regards clinical efficacy, atypical antipsychotic medications have a preferred side effect profile and lesser drop-out rate from trials. Obviously, this is extremely important as treatment adherence is key to successful remission of psychotic symptoms and also in some case prevent relapse of illness. Treatment with olanzapine, risperidone, and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidemia. Adolescents may respond better to standard-dose as opposed to lower dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trial should be longer term and have uniform ways of reporting side effects.Key words: atypical antipsychotic, medications, adolescents, psychosis, systematic review, meta-analysis, young people, pharmacology, schizophrenia     

Antipsychotics in bipolar disorders

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.     

Lithium treatment of acute mania in adolescents: a placebo-controlled discontinuation study

OBJECTIVE: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. METHOD: In this discontinuation study, participants received open treatment with lithium at therapeutic serum levels (mean 0.99 mEq/L) for at least 4 weeks. Responders were randomly assigned to continue or discontinue lithium during a 2-week double-blind, placebo-controlled phase. This study had 80% power to detect a 40% difference in exacerbation rates between groups (10% on lithium versus 50% on placebo). RESULTS: Twenty-three of 40 protocol participants (57.5%) experienced a clinically significant symptom exacerbation during the 2-week double-blind phase. However, the slightly lower exacerbation rate in the group maintained on lithium (10/19 or 52.6%) versus the group switched to placebo (13/21 or 61.9%) did not reach statistical significance. CONCLUSIONS: This study does not support a large effect for lithium continuation treatment of adolescents with acute mania, mostly due to the unexpectedly high rate of exacerbations in the group that continued on lithium. Further studies are warranted to clarify whether acute mania in adolescents is lithium responsive.     

奥氮平合并碳酸锂治疗女性急性躁狂发作的疗效及依从性

目的探讨使用奥氮平、利培酮、氯氮平3种非典型抗精神病药分别合并碳酸锂治疗女性躁狂发作疗效和院外服药依从性。方法按照随机的原则将84例女性患者分为3组,分别使用奥氮平、氯氮平、利培酮合并碳酸锂治疗,在急性期不少于4周的住院期间使用Bech—Rafaelsen躁狂量表（BRMS）、临床总体印象量表（CGI）评估疗效;院外治疗期8周内,应用在Morisky问卷基础上改进的自编依从性问卷对患者及其家属进行调查。结果住院期间奥氮平组起效时间中位数为3d,明显早于利培酮组的（7d）（Z=4．75,P〈0．01）;奥氮平组与氯氮平组（3d）的起效时间差异无统计学意义;治疗2周、4周后奥氮平组BMRS减分值与氯氮平组相当（Z=0．54、0．67,P=0．40、0．49）,而大于利培酮组（Z=3．04、1．98,P〈0．01、P=0．04）。随访期间奥氮平组服药依从性评分高于其他两组。结论奥氮平应用于女性急性躁狂发作患者起效迅速,维持治疗时服药依从性良好,其常见不良反应为过度镇静、头晕和体质量增加。     

Lithium balance in mania

Lithium balance studies were performed in 19 patients suffering from mania and 6 patients suffering from depression. The following results were obtained: (1) The mean daily requirement for lithium in the manic patients was 52 mM, in those with depression 30 mM (additional requirement in manic patients 73%). (2) Renal elimination of lithium, after optimal blood lithium levels had been reached, was 76% in mania and 97% in depression (retention in manic patients 21%). (3) In mania there was an unchanged lithium half-life time (12-13.5 h). (4) In mania and depression no significant differences in lithium and creatinine clearance were noted. (5) Standard diet or unrestricted sodium chloride administration did not significantly influence the lithium requirement or lithium retention. After exclusion of a renal or dietetic cause for increased lithium requirement or retention during mania, the existence of a 'lithium pool' dependent on the presence of a manic psychosis seems probable. As a result of this, somatic influences on endogenous psychosis have to be taken into account.     

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine–fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.

     

Spectrum of effectiveness of valproate in neuropsychiatry

Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.     

Observational study designs for bipolar disorder — What can they tell us about treatment in acute mania?

Randomised controlled trials may have generalisability limitations when applied to the complex treatment of patients with bipolar disorder. Observational study designs can inform us about the diversity of bipolar disorder treatment in naturalistic settings. The aim of this paper was to describe the treatments prescribed for acute mania in a large prospective observational study of bipolar disorder. Patients with a manic/mixed episode were enrolled in EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) if they initiated or changed oral medication with antipsychotics, lithium and/or anticonvulsants. The use of monotherapy or combination therapy for treatment of acute mania, concomitant medications and rate of treatment switching during the 12-week acute treatment phase were assessed. Of the 3459 patients, 36% were treated with one drug and 64% with combination therapy. 55% of patients initiating combination therapy started on an atypical antipsychotic plus lithium or an anticonvulsant. Patients prescribed combination therapy at baseline were more clinically severe, were more often treated as inpatients and had more manic episodes in the previous year compared with the monotherapy group. Treatment switching occurred in 54.4% of patients over the 12-week acute phase. Many patients were taking at least one concomitant medication at baseline (69.4%) and week 12 (50.5%). The results of this observational study show that treatment for mania is complex with multiple combinations of treatment and frequent switching during an acute episode.     

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.     

Antidepressant-associated switches from depression to mania in severe bipolar disorder

OBJECTIVES: To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant (AD) treatment by examining bipolar patients with psychosis early in their illness course. METHODS: A multi-facility cohort of 123 first-admission inpatients, aged 15-60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was followed for four years, and 76 individuals experienced at least one episode of depression. Frequency of and risk factors for switches from depression to mania, time to switch, and duration of the subsequent manic episode were examined in relation to AD use (with anti-manic and/or antipsychotic medications). RESULTS: The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had more depressive episodes and spent more time depressed than non-users. A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode (20%). The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs. None of the risk factors (age of onset 相似文献   

碳酸锂结合氟哌啶醇致恶性综合征(英文)

一名39岁的女性双相障碍患者因再次出现伴精神病性症状的躁狂发作而住院,总病程20年。用常规剂量的碳酸锂和氯氮平治疗。入院3天后,患者出现攻击行为,并拒绝服药,因而停用氯氮平口服,予氟哌啶醇肌注。3天后,患者出现高热以及其他恶性综合征的表现,如大量出汗,肢体肌肉痉挛、震颤,肌强直以及意识障碍。立刻停用氟哌啶醇和锂盐,对症支持治疗,同时用多巴胺激动剂溴隐亭治疗。恶性综合征的症状在3天内缓解,但精神病性症状依然很严重。继而使用丙戊酸钠和奥氮平治疗,未再出现恶性综合征。又治疗1个月后,患者康复出院。过去有若干个病例也与此类似,这些病例提示抗精神病药物合并锂盐治疗引起恶性综合征的风险可能比单用一种抗精神病药物要高。当然病例报告本身无法证实这一点。