The effect of the first manic episode in affective disorder: a case register study of hospitalised episodes.

BACKGROUND: It is poorly understood how the course of illness in depressive patients is affected by a manic episode. METHOD: The course of hospitalised episodes was compared for patients with depressive episodes only, patients who presented with a manic or circular first episode and patients who presented with a depressive first episode and later developed mania. The Danish psychiatric central register was used as a study base, including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: A total of 17,447 patients presented with a depressive first episode and 2903 patients with a manic or circular first episode. Among the 17,447 depressive patients, 762 patients presented with mania at later episodes (4.4%). Younger age at onset was associated with increased risk of developing mania. Patients who had a late first manic episode had the same rate of subsequent recurrence as patients with mania at first episode and this rate was higher than the rate of recurrence for patients who remained having depressive episodes only. Time since first manic episode was without importance in relation to the risk of subsequent recurrence. CONCLUSION: Patients who present with depression and later develop mania have from onset the same risk of recurrence as initially bipolar patients. LIMITATION: The data relate to admissions rather than episodes. CLINICAL RELEVANCE: Younger patients who present with depression have increased risk of developing bipolar disorder.     

Effects of symptomatic severity on elevation of plasma soluble interleukin-2 receptor in bipolar mania

BACKGROUND: Circulating soluble interleukin-2 receptors (sIL-2Rs) and soluble interleukin-6 receptors (sIL-6Rs) are stable immune measures. Elevated plasma sIL-2R levels are present in patients with schizophrenia, major depression, and bipolar mania, but not with minor psychiatric disorders. The increased plasma sIL-2R levels are state-dependent in bipolar mania. However, altered production of plasma sIL-6R and the effects of clinical characteristics on plasma sIL-6R and sIL-2R levels in bipolar disorder remains uncertain. METHODS: Plasma sIL-2R and sIL-6R levels were measured in 31 Taiwanese bipolar manic (DSM-IV) patients with Young Mania Rating Scale (YMRS) scores of > or =26 as well as during the subsequent remission (YMRS< or =12), and equal numbers of age- and gender-matched healthy controls. The relationships of clinical variables such as age, age of onset, smoking, medication status, coexisting psychotic features, number of prior episodes, duration of illness, presence of depression before or following the manic episode, and manic severity to plasma sIL-2R and sIL-6R levels in acute mania along with remission were examined. RESULTS: Plasma sIL-2R but not sIL-6R levels were significantly higher in acute mania than in subsequent remission (P<0.05) and controls (P<0.0005). In acute mania, the plasma sIL-2R levels were significantly correlated to YMRS scores (r=0.34, P<0.05). The remaining clinical variables had no effect on plasma sIL-2R and sIL-6R levels in acute mania or remission. There was a significantly positive relationship between the reduction of plasma sIL-2R levels from the acute to follow-up measurements (DeltasIL-2R) and symptomatic improvement of acute mania (DeltaYMRS) (r=0.61, P<0.001). Limitations: Our sample included medicated and unmedicated patients in acute mania. The psychotropic medication may have divergent effects on the plasma sIL-2R levels in acute mania and subsequent remission. CONCLUSIONS: Elevation of plasma sIL-2R but not sIL-6R levels in bipolar mania supports the idea that the immunomodulatory mechanism may vary in different psychotic disorders. In contrast to being a trait marker in schizophrenia and depressive disorder, plasma sIL-2R levels may be considered a biological indicator of manic severity in a group of bipolar affective patients.     

Recurrence rates of bipolar disorder during the postpartum period: a study on 276 medication-free Italian women

The postpartum period is considered a time of heightened vulnerability to bipolar disorder. The primary goal of this study was to examine the frequency and the polarity of postpartum episodes in a clinical sample of women with bipolar disorder who were medication-free during their pregnancies. In addition, we sought to examine whether there are differences in terms of clinical features of bipolar disorder between women with and without postpartum episodes. Lastly, we analyzed the potential relationship between polarity of the postpartum episodes and clinical features of bipolar disorder. The presence/absence of postpartum episodes and their characteristics were obtained from medical records of 276 women with bipolar disorder who were medication-free during their pregnancies. Two hundred seven women (75.0 %) had a history of one or more postpartum mood episodes: depressive (79.7 %), (hypo)manic (16.4 %), or mixed episodes (3.9 %). Psychotic symptoms during postpartum episodes were associated with depression in 37 (22.4 %) patients, with mania in 19 (67.8 %) patients, and with mixed episodes in 7 (87.5 %) patients. Postpartum manic and mixed episodes were significantly associated with type I disorder and with psychotic features. Our findings indicate high risk of clinically ascertained mood episodes during postpartum period in bipolar women who are not treated during pregnancy.     

Rapid versus non-rapid cycling as a predictor of response to olanzapine and divalproex sodium for bipolar mania and maintenance of remission: post hoc analyses of 47-week data

BACKGROUND: Rapid cycling in bipolar disorder has been associated with greater morbidity. We examine whether rapid cycling affects treatment response to olanzapine or divalproex in acute mania. METHODS: A post hoc analysis of a 47-week, randomized, double-blind study compared olanzapine (5-20 mg/day) to divalproex sodium (500-2500 mg/day) for bipolar manic or mixed episodes (N=251). Young Mania Rating Scale (YMRS) scores > or = 20 were required for inclusion. Patients were classified at study entry as "rapid cyclers" if they experienced > or = 4 episodes within the last year. A repeated measures analysis of variance was used to analyze YMRS change from baseline. RESULTS: A significant three-way interaction (cycling frequency by medication by visit) was found when modeling change in YMRS total scores. For patients with bipolar I disorder identified as rapid cyclers, mania improvement across the trial did not differ significantly between treatment groups (p=0.181). Among non-rapid cyclers, olanzapine-treated patients had significantly greater YMRS improvement than divalproex-treated patients across the trial (p<0.001) and at most time points. Among olanzapine-treated patients, non-rapid cyclers experienced numerically greater YMRS improvement than rapid cyclers throughout the trial; statistically significant differences occurred at weeks 11, 15 and 39. In contrast, among divalproex-treated patients, YMRS scores were significantly better in rapid cyclers than non-rapid cyclers during the first two study weeks but were comparable thereafter. A similar pattern was seen in Clinical Global Impressions-Mania Severity scores. Hamilton Depression scores in rapid versus non-rapid cycling patients differed at some time points but not over the entire trial and differences by cycling status were not treatment-specific. LIMITATIONS: Apart from the post hoc nature of the analyses, there were high dropout rates in both groups, and cycle frequency was not taken into account. CONCLUSIONS: Rapid cycling patients did less well over long-term treatment than non-rapid cycling patients. Among rapid cycling patients, olanzapine and divalproex appear similarly effective against manic symptoms; however, among non-rapid cycling patients, olanzapine-treated patients experienced superior mania improvement. Olanzapine-treated, non-rapid cyclers experienced greater mania improvement than rapid cyclers. The converse was true of divalproex-treated patients early in treatment.     

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.     

Use of olanzapine in dysphoric mania

BACKGROUND: The simultaneous presentation of both manic and depressive symptoms has long been recognized. Nevertheless, a variable prevalence of dysphoric mania has been reported. The aim of this study was to estimate the prevalence of dysphoric mania among hospitalized patients and to assess the effectiveness of olanzapine in this type of patients. METHODS: Eighty-six patients who met DSM-IV criteria for mania were evaluated at admission with a protocol that included McElroy's criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633]. Treatment was administered according to clinical need, using mood stabilizers combined with antipsychotics. Sequential assessments were conducted throughout the study. RESULTS: Forty-four patients (51.2%) fulfilled McElroy's criteria for dysphoric mania. Fourteen of these dysphoric patients were treated with olanzapine in combination with mood-stabilizers. All patients improved in manic symptoms but patients treated with olanzapine improved significantly more than those treated with other antipsychotics in depressive symptoms. LIMITATIONS: The lack of randomization is a methodological limitation of this study, so these findings should be considered as preliminary. CONCLUSIONS: Dysphoric symptoms are common in this population of manic patients. Olanzapine in combination with mood-stabilizers may be effective in these patients. Additional controlled studies are needed to replicate these results.     

Course of bipolar disorder in eastern India.

The life course of affective episodes was determined for 95 consecutively admitted patients from eastern India fulfilling RDC criteria for definite mania during the current episode, using SADS-L interviews. There was a significantly greater frequency of manic compared to depressive relapses. Presentation as recurrent mania was very common. The total numbers of affective and manic episodes were significantly higher among those with recurrent mania and in cases where the first illness episode was manic.     

Lifetime manic spectrum episodes and all-cause mortality: 26-year follow-up of the NIMH epidemiologic catchment area study

Background

While evidence suggests that depression is associated with medical morbidity and mortality, the potential role of mania has received less attention. This analysis evaluated the association between manic spectrum episodes and risk of all-cause mortality over a 26-year follow-up in a population-based study.

Methods

Participants included 14,870 adults (mean age 48.2±20.3; 58.2% female; 31.1% non-white) from four sites of the Epidemiologic Catchment Area Study who completed the Diagnostic Interview Schedule (DIS) mania assessment between 1980 and 1983 and had vital status data available through 2007. Participants were grouped into four mutually exclusive categories based on DIS mania assessment: (1) manic episode (n=46); (2) hypomanic episode (n=195); (3) sub-threshold manic symptoms (n=1041); and (4) no manic spectrum episodes (n=13,588). To determine vital status, participants were matched with the National Death Index. Participants with manic spectrum episodes were compared to those without such episodes with regard to mortality after 26 years.

Results

After adjusting for major depressive symptoms and demographic differences, odds of mortality at follow-up for participants with lifetime manic spectrum episodes in the 30–44 and 45–64 year age cohorts at baseline were higher than those with no lifetime manic spectrum episodes in the same age cohorts (OR=1.39, 95% CI=[1.00, 1.93] and OR=1.41, 95% CI=[1.02, 1.95] respectively).

Conclusions

History of lifetime manic spectrum episodes in early to mid adulthood is associated with increased risk of all-cause mortality in mid to late life.

Limitations

Future studies of mania and mortality should evaluate specific causes of mortality.     

Subtypes of manic episodes according to ICD-10-prediction of time to remission and risk of relapse

BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of hypomania, mania without psychosis and mania with psychosis has not been investigated. METHODS: All patients who got a diagnosis of a single hypomanic episode, single manic episode without psychosis or single manic episode with psychosis in a period from 1994 to 1999 at the first discharge ever in Denmark were identified. The time to discharge from first admission and the risk of relapse leading to readmission were compared for the three groups of patients. RESULTS: Totally, 41 patients with a hypomanic episode, 149 patients with a manic episode without psychotic symptoms and 202 patients with a manic episode with psychotic symptoms at first discharge ever were identified. Patients with mania and psychotic symptoms were admitted longer than patients with mania without psychosis, and patients with mania without psychosis were admitted longer than patients with hypomania. No differences were found in the risk of relapse leading to readmission between the three groups of patients. LIMITATIONS: The results apply to hospitalised patients only. CONCLUSIONS: The ICD-10 subclassification of manic episodes does only partially predict long-term outcome.     

Relevance of the catatonic syndrome to the mixed manic episode

BACKGROUND: Catatonic symptoms have been associated with mixed mania in the older psychiatric literature, however, to date no systematic studies have been performed to assess their frequency in these patients. METHOD: Ninety-nine patients with bipolar disorder manic or mixed episode were assessed for the presence of catatonia. RESULTS: Thirty-nine patients fulfilled criteria for mixed mania of whom 24 were catatonic. Among the patients with pure mania, only three were catatonic. Eighteen catatonic patients with mixed mania required admission to the acute care unit (ACU). LIMITATIONS: Our findings only apply to severely ill patients with mixed mania who require ACU admission. Nevertheless, it is important to know, that the likelihood of overlooking catatonia in less severely ill patients with mixed mania is low and that it does not need to be routinely assessed on a general ward. CONCLUSIONS: Catatonia is frequent in mania and linked to the mixed episode. Catatonia in mixed mania is likely to be found among the severely ill group of patients with mixed mania, who require emergency treatment.     

Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: A meta-analysis of placebo-controlled trials

Background

The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo.

Methods

A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990–2012, was performed using the terms ‘atypical antipsychotics’, ‘SGA’, ‘mixed episodes’, ‘dysphoric mania’ and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3–6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit.

Results

SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (−0.41, 95% CI −0.53, −0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (−0.30, 95% CI −0.47, −0.13; p<0.001) compared to placebo in two trials reporting this information.

Limitations

Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately.

Conclusions

SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.     

Unipolar mania: a distinct disorder?

BACKGROUND: This study aimed to identify the differences between unipolar mania and classical bipolar disorder. METHODS: Patients with at least four manic episodes and at least 4 years of follow-up without any depressive episodes were classified as unipolar mania. This group was compared to other bipolar-I patients defined according to DSM-IV regarding their clinical and socio-demographic variables. RESULTS: The rate for unipolar mania as defined by the study criteria was found to be 16.3% in the whole group of bipolar-I patients. Unipolar manic patients tended to have more psychotic features and be less responsive to lithium prophylaxis compared to other bipolar-I patients. LIMITATIONS: Because it was a retrospective study, there may be some minor depressive episodes left unrecorded in the unipolar mania group despite careful and thorough investigation. In addition, even with our fairly strict criteria for the diagnosis of unipolar mania, the possibility of a future depressive episode cannot be excluded. CONCLUSIONS: Unipolar mania may be the presentation of a nosologically distinct entity.     

Expressed emotion versus relationship quality variables in the prediction of recurrence in bipolar patients

BACKGROUND: The expressed emotion (EE) construct has predicted clinical outcomes in schizophrenia and depression, but few studies have been conducted with bipolar patients. Moreover, there is a particular dearth of information regarding the prediction of depressive versus manic episodes in bipolar patients. Questions also remain about the utility of EE compared to other variables (perceived criticism, relationship negativity, and chronic strain in close relationships) that more directly evaluate interpersonal stress and about specific predictions of mania or depression. METHODS: Forty-seven outpatients with bipolar I disorder participated in a 1-year longitudinal study. A close collateral of the patient completed the Five Minute Speech Sample (FMSS) to assess EE, and participants completed perceived criticism and negativity ratings of collaterals. Clinical outcomes and chronic interpersonal stress were assessed by interview at 3-month intervals. RESULTS: High EE predicted depressive, but not manic recurrence. Other variables of close interpersonal relationships were not significant predictors of recurrence. LIMITATIONS: Participants nominated collaterals, and those who did not have such a confidant were excluded. CONCLUSIONS: The FMSS was sensitive to even mild negativity by the collateral that predicted later depressive episodes. This is the first study to demonstrate polarity-specific effects of EE on the prediction of recurrence in bipolar disorder.     

Evaluating the inter-episode stability of depressive mixed states

BACKGROUND: Depressive mixed state (DMX) is understudied, although this diagnostic concept may be of clinical and theoretical importance. Our goal was to provide preliminary evidence of the inter-episode stability of DMX. The inter-episode stability is known to be an important validator for establishing a distinct clinical entity. METHODS: Out of depressive patients consecutively hospitalized at our institute, those who experienced two or more hospitalizations due to discrete depressive recurrences during a 6-year period were selected. All depressive episodes were directly observed and assessed using a standardized rating instrument in terms of eight intra-episode manic symptoms (flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Assessments for subsequent episodes were performed blindly to those for previous episodes within each patient. RESULTS: The inter-episode stability of categorical DMX diagnoses and the number of intra-episode manic symptoms was moderate but significantly high. Approximately 50% of patients with DMX in the index episode obtained a DMX diagnosis in the second episode. Approximately 40% of the total variance of the number of intra-episode manic symptoms was explained by agreements across several depressive episodes. Depressive patients who experienced a diagnostic switch from unipolar to bipolar disorder had a higher frequency of DMX and a greater number of intra-episode manic symptoms in the index as well as subsequent episodes. LIMITATIONS: All consecutive patients were not followed up. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: The inter-episode stability of DMX may not be so high as is required for establishing a distinct clinical entity. However, the findings strongly suggest that some depressive patients have a long-lasting liability to DMX. It is important to determine whether such a liability to DMX is mediated by affective temperaments, as was originally hypothesized by Akiskal [J. Clin. Psychopharmacol. 16 (1996) 4S-14S]. DMX may be a risk factor to the diagnostic switch from unipolar to bipolar disorder.     

The identification of unipolar mania subtype based on anxiety comorbidity

Background

Unipolar mania is a controversial topic. Clinical research has focused on establishing specific characteristics that allow it to be distinguished from bipolar disorder (BD).

Methods

Experienced and carefully trained clinicians evaluated a clinical sample of 298 patients with bipolar disorder using structured instruments to analyze the clinical and socio-demographics differences between people with manic episodes over the course of a 15-year illness compared with participants with histories of manic and depressive episodes.

Results

According to adopted criteria, 16 (5.6%) participants presented unipolar mania (UM) and 282 participants presented manic and depressive (MD) phases. UM patients reported significantly more hospitalizations and medications, as well as more frequent psychosis at the first episode in the UM group than compared to the MD group. The UM group showed worse overall functioning, although differences in mood status between groups were not identified. Comorbid anxiety disorders and anxiety symptoms occurred significantly less frequently in the UM group.

Limitations

Because of the cross-sectional design, determining causal relationships was not possible. Furthermore, the retrospective nature of the UM diagnosis could not exclude a future depressive episode.

Conclusions

The presence of anxiety disorders can differentiate patients with unipolar mania from those with bipolar mania.     

Economic,clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial

INTRODUCTION: The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania. METHODS: Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed. RESULTS: During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension. CONCLUSION: From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.     

The feasibility of self-assessment of dysphoric mania in the French national EPIMAN study

BACKGROUND: There is presently considerable uncertainty on how to best assess mixed mania. The present contribution explores the feasibility of discriminating manic and dysphoric manic states on the basis of self-rating in the acute phase of the illness. METHODS: In the French four-site national EPIMAN study of 104 patients devoted to the clinical evaluation and subclassification of mania, we used the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self-assessment format. The study was conducted on consecutive patients hospitalized for an acute DSM-IV mania. The severity of mania was measured by the Beigel-Murphy scale (MSRS) assessed by psychiatrists. When mania abated, temperaments according to Akiskal and Mallya were administered in their French version. RESULTS: Principal component analysis revealed a general factor explaining 33% of the variance and, after rotation, seven factors defining different dimensions of the phenomenology of mania. The factorial scores, as well as the dimensional scores of the Carrol-Klein model significantly distinguished pure versus dysphoric mania made on clinical grounds. Gender seemed to influence two factors: high 'anxious-depressive' score in females (which is in line with female overrepresentation in mixed mania), vs. high score in males on the 'gregariousness' factor (which represents social disinhibition of the hyperthymic temperament known to be more prevalent in men). LIMITATION: Cross-sectional correlational study in need of longitudinal validation. CONCLUSIONS: EPIMAN data deriving from a national clinical population showed the feasiblity and face validity of self-assessment in acute mania, in particular its dysphoric subtype. Temperament in women seemed to contribute to the genesis of mixed (dysphoric) mania in accordance with Akiskal's hypothesis of opposition of temperament and polarity of bipolar episodes in mixed states. Self-assessment was capable of capturing accurately the subthreshold depressive symptomatology of mixed mania, which can be missed in hetero-evaluation by hasty clinical interview.     

Prodromes, coping strategies and course of illness in bipolar affective disorder--a naturalistic study.

BACKGROUND: Psychosocial interventions for bipolar patients often include teaching patients to recognize prodromal symptoms and tackle them early. This prospective study set out to investigate which bipolar prodromal symptoms were reported frequently and reliably over a period of 18 months. Furthermore, we have also investigated which types of coping strategies were related to good outcome. METHOD: Forty bipolar patients were interviewed for their bipolar prodromal symptoms and their coping strategies at recruitment and 18 months later. Patients were also assessed as to whether they had experienced relapses. RESULTS: Bipolar patients were able to report bipolar prodromal symptoms reliably. Mania prodromal symptoms tended to be behavioural symptoms. A quarter of patients reported difficulties in detecting depression prodromes, which tended to be more diverse and consisted of a mix of behavioural, cognitive and somatic symptoms. Significantly fewer patients who reported the use of behavioural coping strategies to curb excessive behaviour during the mania prodromal stage experienced a manic episode. Similarly, significantly fewer patients who reported the use of behavioural coping strategies experienced depression relapses. How well patients coped with mania prodromes predicted bipolar episodes significantly when the mood levels at baseline were controlled. Ratings of how well subjects coped with mania prodromal symptoms also predicted manic symptoms significantly at T2 when manic symptom at T1 was controlled. CONCLUSION: Our study suggests that bipolar patients are able to report prodromal symptoms reliably. It is advisable to teach patients to monitor their moods systematically and to promote good coping strategies.     

Aripiprazole monotherapy in the treatment of bipolar disorder: a meta-analysis

Introduction

Aripiprazole is approved for the acute and maintenance treatment of manic and mixed episodes associated with bipolar I disorder. The aim of the present work was to review and meta-analyze the findings of all the available randomized double-blind controlled trials (RCTs) on the efficacy of aripiprazole in the treatment of bipolar disorder.

Material and methods

Aripiprazole RCTs were identified with a systematic search of MEDLINE and repositories. Standard meta-analytic techniques were applied.

Results

Two thousand three hundred and three patients took part in the aripiprazole acute mania RCTs. At week 3 the pooled aripiprazole vs. placebo effect size was 0.34 and the NNT was 6 for response and 14 for remission. On average, response started at day 3. Suicide rates were negligible for all groups in mania but they were not reported in the acute depression trials. The meta-analysis of acute bipolar depression RCTs revealed a significant difference at week 8 with a weak effect size equal to 0.17. The analysis of maintenance data suggest that the median survival time for the aripiprazole group was not evaluable (very long), while the median survival time for placebo was 118-203 days depending on the clinical subpopulation.

Discussion

The current meta-analysis supports the usefulness of aripiprazole during all phases of bipolar illness. Its effect against acute bipolar depression is weak and the efficacy during the maintenance phase is proven only against new manic episodes in patients with an index manic episode who had previously responded to aripiprazole during the acute phase.