Effects In Bipolar Depression Research Articles

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites

BackgroundWhile theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. MethodsThirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3–4 days posttreatment (T1) and 10–11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. ResultsAlthough the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LimitationsThe modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10–11 days, whereas similar studies usually follow up for at least one month. ConclusionMore research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Lurasidone: an antipsychotic with antidepressant effects in bipolar depression?

Lurasidone is a new serotonin-dopamine antagonist atypical antipsychotic which also appears to be effective in bipolar depression. This paper will briefly review the evidence concerning lurasidone. Lurasidone is an antagonist at dopamine D2, serotonin 5-HT2 and 5-HT7, and partial agonist at 5HT1a receptors; it has no anticholinergic or antihistaminic activity. Rapidly absorbed, it has a half-life of 18 ± 7 hours, will reach steady state in five days and is taken at night with food (absorption is halved on an empty stomach). It is hepatically metabolised with some potential for interactions. Lurasidone is an effective antipsychotic in acute schizophrenia, and non-inferior to quetiapine but not risperidone in 12-month studies. Lurasidone may cause mild sedation, nausea, agitation, insomnia and akathisia (especially at initiation). Risks for weight gain, hyperprolactinaemia and QTc prolongation are low. Lurasidone has demonstrated antidepressant efficacy both as monotherapy and in addition to lithium or valproate in bipolar depression, of a comparable degree to that seen with the combination of olanzapine and fluoxetine. Lurasidone appears to be a "metabolically-friendly" antipsychotic for schizophrenia where weight gain and hyperprolactinaemia are of concern, and may also prove useful in bipolar depression (although not approved for this condition in Australia).

Neuropsychological deficits in bipolar depression persist after successful antidepressant treatment

BackgroundBipolar disorder is a common disabling illness with a lifetime morbid risk of approximately 4%. Neuropsychological deficits constitute enduring trait-like features in bipolar disorder, are associated with each phase of the illness and persist also in euthymia. Total sleep deprivation (TSD) has been shown to cause rapid and sustained antidepressant effects in bipolar depression and to revert the biased self description and speed of information processing present in these patients. The aim of the study was to assess neuropsychological performances first in a sample of bipolar patients during a depressive episode compared to healthy controls and secondly to investigate if TSD treatment would change cognitive performances. MethodsOne-hundred bipolar patients and 100 healthy controls were evaluated through the Brief Assessment of Cognition in Schizophrenia, 42 patients were assessed before and after TSD treatment. ResultsBipolar patients obtained significantly lower domain scores across the entire battery compared to healthy subjects. Cognitive deficits persisted in each function despite a clinical improvement of depressive symptomatology. LimitationsLimitations of the study include issues such as generalizability, possible undetected past comorbidities, population stratification and ongoing medication. ConclusionsThis is the first study of the effect of TSD treatment on cognitive performance. TSD treatment improved clinical symptoms but not cognitive deficits however bipolar patients did not experience the well known worsening of performance observed in healthy controls after sleep loss.

Lamotrigine in the treatment of recurrent brief depression

Recurrent brief depression is a well-recognized subtype of depressive illness with brief episodes of depression alternating with periods of euthymia. The symptoms are often severe, with frequent association to suicidal ideation. Literature suggests frequent nonresponse to first-line antidepressants. Lamotrigine is an anticonvulsant with antidepressant properties, and reported effectiveness in bipolar depression. We report on two patients with recurrent brief depression, nonresponsive to selective serotonin reuptake inhibitors and venlafaxine, and who responded to therapeutic doses of lamotrigine.

Dopaminergic augmentation of sleep deprivation effects in bipolar depression

Total sleep deprivation (TSD) has been used in association with lithium salts and with serotonergic and noradrenergic antidepressants, leading to sustained improvements in patients affected by major depression. Current theories on the neurobiological mechanism of action of TSD propose a major role for enhanced dopamine activity. To test the clinical relevance of dopaminergic enhancement in TSD, we treated a homogeneous sample of 28 bipolar depressed patients with three cycles of TSD combined with placebo or with the dopaminergic antidepressant amineptine. Changes in mood over time were rated with self-administered visual analogue scales and with the Montgomery–Åsberg Depression Rating Scale. Patients showed improved mean daily-mood scores after TSD, an effect that was highest at the first cycle and decreased with treatment repetition. Amineptine enhanced the effects of TSD on perceived mood during the first two TSD cycles, but patients in the placebo and amineptine groups showed comparable results at the end of the treatment. Despite its theoretical importance, the clinical usefulness of combining TSD with a dopaminergic agent must be questioned.