Depressive Episodes In Patients Research Articles

Paroxetine with pindolol augmentation: A double-blind, randomized, placebo-controlled study in depressed in-patients

Pindolol, a 5-HT1A autoreceptor antagonist, given in combination with selective serotonin reuptake inhibitors (SSRIs), may enhance and/or accelerate the therapeutic efficacy of SSRIs. Fifty patients, meeting ICD-10 criteria for major depressive disorder or bipolar depression, were enrolled in our randomized, placebo-controlled, double-blind trial. One group received paroxetine plus pindolol (2.5 mg t.i.d.), and the other group received paroxetine plus placebo. The proportion of patients with sustained response (≥ 50% reduction of baseline HAM-D 17 score maintained until the endpoint; p = 0.252) and the proportion of patients with remission (HAM-D 17 ≤ 8 at last visit; p = 0.769) did not differ significantly between the two treatment groups. However, a significantly greater proportion of patients who were not previously treated with antidepressants ( n = 15; p = 0.041) and of patients with bipolar depression ( n = 11; p = 0.015) had a sustained response in the paroxetine plus pindolol group compared to the paroxetine plus placebo group; furthermore there was a trend for first episode depressed patients to have a greater response in the paroxetine plus pindolol group ( n = 12; p = 0.071). Summarizing, the entire study population showed no antidepressive benefit from pindolol augmentation. Nevertheless patients with bipolar depression irrespective of previous treatments and duration of illness, and unipolar patients not previously treated demonstrated a significant benefit from pindolol augmentation.

The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode

Background and aimsStudies have already pointed out a possible pathophysiological role of oxidative and antioxidative molecules in bipolar disorder. We aimed to evaluate the activity and levels of antioxidant superoxide dismutase (SOD), and oxidant nitric oxide (NO), in bipolar I depressive episode (BD-DE) patients in a prospective design. Method30 BD-DE patients, diagnosed according to DSM IV, and 30 healthy volunteer controls were included. The serum levels of NO and SOD have been studied when admitted to hospital (1st) and on the 30th days. Clinical outcome was measured by Hamilton Depression Scale (HAM-D). The patients were allowed to have their treatments. One patient was dropped out due to insufficient sampling. ResultsAs in the previous studies, NO 1st day levels were significantly higher in patients and SOD 1st day activity was significantly low (p<0.01). NO levels significantly decreased (p<0.01) and normalized, as SOD activity significantly increased but did not reach to the controls' levels (p<0.01) on the 30th day. ConclusionDespite normalized NO levels, persistent low SOD activity might point out an oxidative imbalance in BD-DE. Chronic low SOD activity may be associated with incapacity of coping with oxidative stress. This research connotes the probable oxidative imbalance in BD-DE and discusses that phenomenon within the continuum of the disease state.

Quetiapine monotherapy in the treatment of patients with bipolar I or II depression and a rapid‐cycling disease course: a randomized, double‐blind, placebo‐controlled study

To investigate the efficacy and tolerability of quetiapine monotherapy in patients with bipolar I or II disorder with a rapid-cycling disease course. Adult patients with a DSM-IV diagnosis of bipolar disorder, most recent episode depressed, with a rapid-cycling disease course from a previously completed multicenter trial randomized to 8 weeks of treatment with quetiapine 600 mg/day (n = 31), quetiapine 300 mg/day (n = 42), or placebo (n = 35) were included in this sub-analysis. The primary efficacy variable was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Quetiapine (600 and 300 mg/day) provided significantly greater mean reductions from baseline to week 8 in the MADRS total score than placebo (-21.1, -20.7 versus -11.6, both p < 0.001) in this patient population. Effect sizes in patients with a rapid-cycling disease course were 1.2 (600 mg/day) and 1.1 (300 mg/day) and were similar for bipolar I (0.98 and 1.22) and bipolar II (1.45 and 0.97) sub-groups. Significant improvements were also noted on the Clinical Global Impression, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire scales. Quetiapine was generally well tolerated with moderate increases in weight and extrapyramidal side effects compared to placebo. The incidence of treatment-emergent mania was similar to placebo. Quetiapine monotherapy (600 or 300 mg/day) is clinically effective and well tolerated in the short-term treatment of depressive episodes in patients with bipolar I or II disorder who have a rapid-cycling disease course.

Long-Term and Preventative Treatment for Seasonal Affective Disorder

Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function. There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1-2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD. Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects.

Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P <or= 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).

A Clinical Approach to Mild Cognitive Impairment

A Clinical Approach to Mild Cognitive Impairment

ECT Anesthesia: The Lighter the Better?

Electroconvulsive therapy (ECT) is a most effective treatment for patients with major affective disorders. The influence of anesthetic drugs on seizure "adequacy" or on treatment success has not been systematically investigated. A bispectral EEG index score (BIS) was used to identify the depth of anesthesia during ECT. Our study included 22 major depressive episode (MDE) patients expanding to 219 ECTs (05/05-01/06) with no limitations of concurrent medication. Fourteen out of the 22 patients showed full remission. Individual number of ECT sessions needed to reach full remission correlated negatively with mean pre-ECT BIS values (p=0.001). Additionally, using a repeated measurement regression analysis significant correlations were found for pre-ECT BIS versus motor response time, seizure concordance, ictal coherence and peak heart rate. The results of our study suggest BIS-levels as a predictor of faster ECT response. Controlling BIS-levels before stimulation may have an additional effect on treatment success.

Regional cerebral glucose metabolism in patients with secondary depressive episodes after fatal pancreatic cancer diagnosis

Background Secondary depression is common in the clinical oncology setting after pancreatic cancer diagnosis, following which the patients have to face the fact that they have a cancer with an extremely poor prognosis. However, the specific pathophysiology remains unclear. The present study examined the regional cerebral glucose metabolism using F18-fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) in antidepressant-naïve pancreatic cancer patients with a depressive episode after their cancer diagnosis and before their cancer treatment. Methods Regional cerebral glucose metabolism in pancreatic cancer patients without any antidepressant medication after the cancer diagnosis was measured with F18-FDG PET. A depressive episode after the cancer diagnosis was defined as including major and minor depressive episodes, and was diagnosed using the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV). The prefrontal and limbic regions were the primary regions-of-interest, and an uncorrected value of p < 0.005 was used as significant. Results Six of 21 pancreatic cancer patients were diagnosed as having a depressive episode. Significantly higher glucose metabolism in depressed patients was found in the subgenual anterior cingulate cortex (sACC) (uncorrected p = 0.002). Limitations There was a small number of subjects, and there were no healthy controls. Conclusions The higher metabolism in the sACC may be associated with the pathophysiology of secondary depressive episodes in patients following pancreatic cancer diagnosis.

Depression and epilepsy: a new perspective on two closely related disorders.

Depression is the most frequent psychiatric comorbidity in epilepsy. Yet, it remains under-recognized and untreated in a significant number of patients. It may mimic primary depressive disorders, but in a significant percentage of patients, depression presents with atypical pleomorphic characteristics. The use of screening self-rating scales may help to identify depressive episodes in patients with epilepsy, but a diagnosis cannot be established by the sole use of these instruments without an additional, in-depth evaluation. Timely recognition and treatment of depression is of the essence in epilepsy patients, as its persistence is an independent predictor of poor quality of life, increased suicidal risk, greater use of health services, and higher medical costs not related to the psychiatric treatment. Neurologists will often find themselves in the position of being the only health care provider available to initiate treatment. Accordingly, they should be well trained to provide psychopharmacologic treatment for major depressive episodes, dysthymic disorders, and minor depression. However, patients with suicidal ideation, psychotic symptoms, or bipolar disorders should be referred immediately to the care of a psychiatrist.

Med Check

Med Check

Second-generation antidepressant discontinuation and depressive relapse in adult patients with bipolar depression: Results of a retrospective database analysis

To date, few postmarketing studies have addressed whether long-term prophylactic treatment with second-generation antidepressants (ADs) delays depressive episodes in patients with bipolar disorder. The aim of this study was to compare the risk of depressive relapse between patients with bipolar disorder who took second-generation ADs>-6 months after depressive remission with those who discontinued AD use early. Using a large US managed-care claims database, continuously enrolled bipolar subjects who took second-generation ADs after a depressive remission were identified between January 1, 1998, and December 31, 2002. Duration of AD and concurrent mood stabilizer use were based on coded diagnoses and pharmacy records. A Cox proportional hazards model was developed to predict time from depressive remission to next depressive relapse with continuous AD use, categorized as either >or=6 months or <6 months. Propensity scoring with greedy matching was used to help balance the observed background covariates and baseline disease severity between groups. Five hundred eighty-nine subjects met the inclusion criteria. A Kaplan-Meer estimate found that the median depressive relapse times for the continuous (ie, >or=6 months) and early discontinuation (ie, <6 months) AD treatment groups were 16.5 and 6.8 months, respectively (P<0.05). The Cox proportional hazards model with propensity score matching identified a significantly lower risk of depressive relapse over a 2-year period among those who continued AD treatment>or=6 months after remission, compared with those who discontinued treatment within 6 months (hazard ratio, 0.61 [95% CI, 0.42-0.88]; continuous vs early discontinuation, P<0.01). Continuous second-generation AD therapy for >or=6 months after depressive remission was associated with a lower risk of depressive relapse over a 2-year period in patients with bipolar depression. Given concerns regarding the risk of AD users with bipolar disorder switching to mania, an optimal prophylactic treatment after depressive remission should balance the risks between manic switching and depressive relapse.

CSF serotonin, 5-hydroxyindolacetic acid and neuropeptide Y levels in severe major depressive disorder

Serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) have been the putative markers of MDD. Neuropeptide Y (NPY) may have an important role in the pathophysiology of major depressive disorder (MDD). However, direct measures of cerebrospinal fluid (CSF) 5-HT and NPY in severe MDD have been lacking. In the present study, we examined CSF 5-HT, 5-HIAA and NPY levels and correlate them with gender and suicidal behavior of severe major depressive disorder. Forty drug-free subjects with a severe major depressive disorder and forty control subjects underwent lumber puncture and psychiatric evaluation. Cerebrospinal fluid levels of 5-HT, 5-HIAA and NPY were assayed by enzyme-linked immunosorbent assay (ELISA) test. The relationships among 5-HT, 5-HIAA, NPY and clinical variables were statistically evaluated. There were no differences between severe major depressive disorder and controls in all parameters measured. In severe MDD group, significantly lower CSF 5-HT and higher 5-HT turnover (5-HIAA/5-HT) were found in female patients compared with male patients. The patients with intense suicidal intents and suicidal attempts had significantly lower CSF 5-HT compared to patients with nonsuicidal intents. Additionally, significantly lower CSF NPY was found in first episode depressed patients compared with recurrent depressed patients. Gender-related difference in CSF 5-HT implied a female preponderance in major depression to some extent. Cerebrospinal fluid 5-HT levels and 5-HT turnover (5-HIAA/5-HT) could be valuable tools for prediction of suicidality and potential markers for evaluating major depressive disorder. NPY was perhaps a marker for first episode depression.

A 24-Week Open-Label Extension Study of Olanzapine-Fluoxetine Combination and Olanzapine Monotherapy in the Treatment of Bipolar Depression

Olanzapine-fluoxetine combination has shown efficacy in the acute treatment of depressive episodes in patients with bipolar I disorder. The present analyses examined the efficacy and safety of longer term treatment with olanzapine-fluoxetine combination or olanzapine monotherapy in a 6-month open-label extension study. 376 patients with DSM-IV bipolar I disorder, depressed, who completed an acute trial entered the open-label study and received 1 week of olanzapine monotherapy (5-20 mg/day). At all subsequent visits, patients could choose between olanzapine monotherapy or olanzapine-fluoxetine combination (6/25, 6/50, or 12/50 mg/day). Three treatment groups were defined retrospectively according to the medication course taken from week 1: olanzapine, olanzapine-fluoxetine combination, or switched. The efficacy measures were the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions-Bipolar Version, and Young Mania Rating Scale. The study was conducted from July 2000 to May 2002. Among patients who started in remission, MADRS total scores did not change significantly from baseline to endpoint in the olanzapine-fluoxetine combination (0.8) or olanzapine (0.3) groups, but increased slightly in the switched (2.3, p = .02) group. For patients who started in nonremission, MADRS total scores decreased significantly in all groups (olanzapine-fluoxetine combination: -5.7, p = .001; olanzapine: -11.6, p = .004; switched: -6.4, p = .015). The majority of patients who entered the study in nonremission achieved remission (MADRS total score < or = 12) during the trial (olanzapine-fluoxetine combination: 66.7%, olanzapine: 64.7%, switched: 62.5%). The overall rate of depressive relapse was 27.4%, and the overall incidence of mania emergence was 5.9%. The present findings suggest that long-term treatment with olanzapine-fluoxetine combination may be a useful option for the management of depressive symptoms and carries a low risk of mania emergence.

Bupropion

Bupropion was initially developed and licensed for the treatment of major depressive disorder in the United States in 1989. It was licensed as a pharmacotherapy for smoking cessation in the United States in 1997 and in the United Kingdom in 2000, and for the prevention of seasonal major depressive episodes in patients with seasonal affective disorder in the United States in 2006. Its main mechanism of action is believed to be via dopamine and noradrenalin reuptake inhibition. In addition to proven clinical efficacy for the treatment of major depression, the prevention of depressive episodes in patients with seasonal affective disorder, and as an aid to smoking cessation treatment, bupropion has demonstrated efficacy for attenuation of symptoms of attention deficit hyperactivity disorder, and more recently it has shown anti-inflammatory action against proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may be implicated in a number of inflammatory diseases such as Crohn's disease. The twice-daily sustained-release formulation has been extensively evaluated for smoking cessation and has shown continuous smoking abstinence rates at one year of the order of 20% across many clinical groups including healthy smokers, and smokers with cardiovascular disease, chronic obstructive airways disease, depression and schizophrenia. Bupropion is well tolerated with side effects including insomnia, headache, dry mouth, dizziness and nausea. Bupropion is a cytochrome p450 2D6 inhibitor and care must be taken when coprescribing with drugs cleared by this enzyme and when coprescribing with drugs that lower seizure threshold. Despite the clinical effectiveness and cost-effectiveness of bupropion as an aid to smoking cessation, its uptake for this indication remains low when compared with nicotine replacement therapy.

Prospective Study of Clinical Predictors of Suicidal Acts After a Major Depressive Episode in Patients With Major Depressive Disorder or Bipolar Disorder

Prospective Study of Clinical Predictors of Suicidal Acts After a Major Depressive Episode in Patients With Major Depressive Disorder or Bipolar Disorder

Prefrontal Cortex and Amygdala Volume in First Minor or Major Depressive Episode After Cancer Diagnosis

Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.

Social Stress in Tree Shrews as an Animal Model of Depression: An Example of a Behavioral Model of a CNS Disorder

Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients. To discover whether this model, besides its "face validity" for depression, also has "predictive validity," we treated subordinate animals with the tricyclic antidepressant clomipramine and found a time-dependent recovery of both endocrine function and normal behavior. In contrast, the anxiolytic diazepam was ineffective. Chronic psychosocial stress in male tree shrews significantly decreased hippocampal volume and the proliferation rate of the granule precursor cells in the dentate gyrus. These stress-induced changes can be prevented by treating the animals with clomipramine, tianeptine, or the selective neurokinin receptor antagonist L-760,735. In addition to its apparent face and predictive validity, the tree shrew model also has a "molecular validity" due to the degradation routes of psychotropic compounds and gene sequences of receptors are very similar to those in humans. Although further research is required to validate this model fully, it provides an adequate and interesting non-rodent experimental paradigm for preclinical research on depression.

The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C>T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B(12) were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P= 0.03). Serum levels of folate, homocysteine and vitamin B(12) did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.

The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C&gt;T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B12 were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P = 0.03). Serum levels of folate, homocysteine and vitamin B12 did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.

Effect of Lamotrigine on Cognitive Complaints in Patients With Bipolar I Disorder

This analysis describes the effects of bipolar I disorder on self-reported neurocognitive measures and remediation of these deficits with lamotrigine therapy. Data were derived from 2 clinical trials designed to assess the efficacy of lamotrigine as maintenance therapy for recently manic (N = 349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week open stabilization phase, patients received lamotrigine as monotherapy or as adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to measure cognitive functioning at baseline and at the end of the open-label phase. To examine the relationship between depressive and manic symptomatology, initiation of lamotrigine, and cognitive functioning, correlational analyses and analyses of covariance were conducted. Bipolar patients in both trials had significant cognitive impairment; however, it was much greater in index episode depressed bipolar patients compared with index episode manic patients. In both studies, substitution of lamotrigine for other psychotropic medications significantly improved the mean scores from baseline to the end of the open-label phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or 35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062) showed similar improvement. Cognitive impairment was significantly correlated with depression symptom severity based on Hamilton Rating Scale for Depression scores (p < .0001). After controlling for change in mood, age, gender, baseline score, duration of illness, and duration of use of other psychotropics, a significant improvement in cognition was observed during the open-label phase when lamotrigine was used as monotherapy/adjunctive therapy. Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity.