Prevention Of Mood Episodes Research Articles

Cariprazine as a maintenance therapy in the prevention of mood episodes in adults with bipolar I disorder.

Cariprazine treats acute manic and depressive episodes in bipolar I disorder (BP-I), but its efficacy in preventing relapse of mood episode remains unknown. In this phase 3b, double-blind, placebo-controlled study, patients with BP-I with acute manic or depressive episodes (each with/without mixed features), were treated with cariprazine 3.0 mg/day during a 16-week open-label treatment period; those who achieved stable remission within 8 weeks and remained stable for at least another 8 weeks were randomized to receive cariprazine 1.5 or 3.0 mg per day or placebo in the double-blind treatment period for up to 39 weeks. The primary efficacy endpoint was time to relapse of any mood episode. Adverse events (AEs) were assessed. Patients (440/896) enrolled in the open-label treatment period achieved stability criteria and were randomized to receive cariprazine 3.0 mg/day (n = 148), cariprazine 1.5 mg/day (n = 147), or placebo (n = 145) in the double-blind treatment period. Relapse rates were 17.9%, 16.8%, and 19.7% in the cariprazine 3.0 mg/day, cariprazine 1.5 mg/day, and placebo groups, respectively. Neither dose of cariprazine was more effective than placebo on the primary outcome (3.0 mg/day: HR = 0.89, [95% CI: 0.5, 1.5]; 1.5 mg/day: HR = 0.83, 95% CI [0.5, 1.4]). The most frequently reported AEs (≥5%) were akathisia, headache, insomnia, and nausea in the open-label treatment period and increased weight and insomnia in the double-blind treatment period. In the open-label and double-blind treatment periods, 7.5% and 1.6% of patients experienced an AE leading to discontinuation. Cariprazine was not superior to placebo in the prevention of relapses in this study. Relapse rates were unusually low in the placebo group. Cariprazine was well-tolerated.

Treatment of Comorbid Psychiatric Disorders with Bipolar Disorder.

Life time psychiatric comorbidities of bipolar disorders are highly prevalent. Anxiety disorders, alcohol-substance use disorders, obsessive-compulsive disorder and attention deficit and hyperactivity disorder are the most common comorbid psychiatric conditions in bipolar disorders. Psychiatric comorbidity of bipolar disorders is strongly associated with poor treatment response, higher recurrence of mood episodes, suicide attempts, rapid-cycling, worse general functioning and quality of life. Therefore, considering the huge impact of comorbidity on the bipolar disorder illness course, treatment is usually challenging. The primary aim of the treatment in psychiatric comorbidity of bipolar disorder should be mood stabilization and prevention of mood episodes. Then, first line treatment options recommended for the specific psychiatric disorders might be preferred for the treatment of bipolar disorder comorbidity. With this rationale, quetiapine can be listed as a first line treatment for anxiety disorders comorbidity in bipolar disorders while serotonergic antidepressants and olanzapine are recommended as second line options. For the treatment of alcohol-substance use disorders comorbidity, first line mood stabilizers such as valproate and lithium and new generation antipsychotic quetiapine seem to be the leading options. Serotonergic antidepressants for obsessive-compulsive disorder and stimulants for the attention-deficit hyperactivity disorders are the key treatment choices. However, both treatment agents might cause to manic switch and mood destabilization. Thus, clinicians should be aware of these complications when prescribing in bipolar disorders comorbidity.

Bipolar Bozukluk Ve Özkıyım / Bipolar Disorder and Suicide

Objective: The risk factors associated with suicidal behaviour in bipolar patients still are not clear. We aimed to evaluate the frequency of suicide attempt, type of suicide attempt and significant clinical characteristics associated with suicide attempts. Methods: One hundred twenty two consecutive patients, from Bipolar Disorder Unit of Cukurova University, Faculty of Medicine, Department of Psychiatry, are included in this study. “Affective Disorders Patient Registry Form” was developed by Bipolar Disorder Unit and SCID-I were used in this study to collect the data. These forms are filled in through interviews with patients and their relatives, and evaluation of inpatient files. Results: The prevalence of suicide attempt was 19.7% in the outpatient group. Lifetime history of suicidal behavior was significantly associated with following characteristics: being a woman, depression as a first episode and indicators of severity of bipolar disorder including duration of illness, duration of untreated illness (latency), number of hospitalization, number of total mood episodes, number of depressive episodes, number of mixed episodes, positive familial psychiatric disorder history. Conclusion: Our study showed that patients with bipolar disorder have a high rate of suicide attempt. Reduction of the duration of untreated illness, prevention of mood episodes, assessment of suicide risk during depressive and mixed episodes should be the main targets of the treatment. Detection of warning signs about suicide among patients with bipolar disorder may help to distinguish the risky group and prevent suicide.

P03-359 Randomized, double-blind, placebo-controlled study of risperidone long-acting injectable in relapse prevention in patients with bipolar I disorder

ObjectivesTo evaluate risperidone long-acting injectable (RLAI) versus placebo in prevention of mood episodes in adults with bipolar I disorder.MethodsA 12-week open-label period with RLAI (N=585) was followed by an 18-month randomized, double-blind period with RLAI (25, 37.5 or 50 mg/2 weeks; N=137) or placebo (N=140); a third group (N=138) was randomized to olanzapine for reference and exploratory comparisons. Primary efficacy endpoint: time to relapse of any mood episode for risperidone LAI vs. placebo in the double-blind period (Kaplan-Meier analysis). Relapse was defined by criteria including DSM diagnosis, further treatment, hospitalisation, or Clinical Global Impression score ≥4 combined with YMRS or MADRS >12.ResultsDosing was fixed during the double-blind period at patients’ final open-label dose (25 mg, 66%; 37.5 mg, 31%; 50 mg, 4%). Time to recurrence (any mood episode) was longer with RLAI versus placebo (log-rank test stratified by region and patient type, p=0.062; stratified by region only, p=0.032); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.587). Discontinuations due to adverse events (AEs) occurred in 2% of patients in the open-label period, and 4% and 1% in the RLAI and placebo groups, respectively, in the double-blind period. The most frequently reported AE in the open-label period was insomnia (15%). During double-blind treatment, the most frequently reported AEs with RLAI were weight increased (24%; placebo, 9%) and insomnia (16%; placebo, 17%).Table 1.Type of recurrenceType of episode, n (%)Risperidone LAI (N=135)Placebo (N=138)All mood episodes52 (38.5)77 (55.8)Elevated mood episode27 (20.0)54(39.1)Hypomanic2(1.5)4 (2.9)Manic17(12.6)43(31.2)Mixed8 (5.9)7(5.1)Depressive25(18.5)23(16.7)ConclusionRLAI significantly delayed time to relapse of elevated mood episodes and was well tolerated.

Treatment of bipolar disorder: New perspectives

Treatment of bipolar disorder (BD) has traditionally focused on alleviation of acute symptoms and prevention of future recurrences. Current treatment guide-lines advocate more or less similar treatment algorithms for all patients. Such approach largely ignores the clinical, genetic, and pathophysiological heterogeneity of BD, which makes certain patients more (or less) likely to respond to specific treatments. Variables such as family history, comorbidity, course of illness, quality and duration of previous remissions, physical and medical comorbidity, and side-effects may help in selecting the most effective treatment for an individual patient, yet their value is not recognized by current algorithms. As well, polymorphisms of specific genes may prove useful in predicting treatment outcome and/or understanding the pharmacological mechanisms of mood stabilization. Novel molecular targets have recently emerged from studies of mechanisms of action of available mood stabilizers. They include inhibitors of protein kinase C, inhibitors of glycogen synthase kinase, or medications modulating glutamatergic neurotransmission. As well, treatment targets are moving beyond acute symptoms and prevention of mood episodes. Cognitive deficits, persistence of residual symptoms, and increased mortality of BD are recognized as important for outcome of BD, yet are not always adequately addressed by traditional treatments.

Differential Efficacy of Olanzapine and Lithium in Preventing Manic or Mixed Recurrence in Patients With Bipolar I Disorder Based on Number of Previous Manic or Mixed Episodes

Bipolar disorder outcome worsens as number of manic episodes increases, suggesting that prevention of recurrent episodes early during the disorder could improve patient prognosis. We investigated treatment efficacy in prevention of mood episodes in patients subgrouped by number of prior manic episodes. This study was a post hoc analysis of data from a multicenter, double-blind, 12-month clinical trial of relapse/recurrence in 431 initially euthymic patients with at least 2 prior manic/ mixed episodes and a DSM-IV diagnosis of bipolar I disorder randomly assigned to olanzapine (5-20 mg/day) or lithium (serum concentration 0.6 to 1.2 mEq/L). Data were collected between August 1999 and June 2002. Patients were subcategorized by illness stage according to number of prior manic/mixed episodes-early stage: 2 prior episodes (N = 53, lithium; N = 48, olanzapine), intermediate stage: 3 to 5 prior episodes (N = 80, lithium; N = 98, olanzapine), and later stage: more than 5 prior episodes (N = 81, lithium; N = 71, olanzapine)-and were evaluated for rates of relapse/recurrence. There were significant effects for treatment (p < .001) and illness stage (p = .006) but no significant interaction (p = .107) on rate of manic/mixed relapse/recurrence. Rates of manic/ mixed relapse/recurrence for olanzapine versus lithium were 2.1% versus 26.4% (p = .008), 13.3% versus 23.8% (p = .073), and 23.9% versus 33.3% (p = .204) for early-, intermediate-, and later-stage groups, respectively. There was no significant effect for treatment (p = .096) or illness stage (p = .731) for depressive relapse/recurrence. Early-stage (but not intermediate-or later-stage) patients had a significantly lower rate of relapse/recurrence of manic/mixed episodes with olanzapine compared to lithium. Thus, olanzapine maintenance therapy may be particularly effective early in the course of bipolar illness.

Lamotrigine: a review of its use in bipolar disorder.

Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure. Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania. Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine. Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.