Patients receiving lithium therapy have a reduced prevalence of neurological and cardiovascular disorders.

A variety of evidence from laboratory and animal studies suggests that lithium has neurotrophic and cytoprotective properties, and may ameliorate or prevent some disease states. We investigated whether such a protective effect can be observed in human psychiatric patients receiving lithium therapy. We carried out a retrospective chart review of 1028 adult psychiatric male and female outpatients attending four lithium clinics in metropolitan New York City. Patients were divided into two groups based on lithium usage, and the prevalence of neurological and cardiovascular disorders was compared. The main outcome measures were the occurrence in the two patient groups of a variety of neurological disorders and myocardial infarction. Odds ratios were calculated to assess the risk of having a disorder for patients receiving lithium compared to patients not receiving lithium: for seizures, the odds ratio was 0.097; for amyotrophic lateral sclerosis, the odds ratio was 0.112; for dementia not otherwise specified, the odds ratio was 0.112; and for myocardial infarction, the odds ratio was 0.30. Logistical regression analysis showed that lithium treatment is a significant negative predictive factor in the prevalence of each of these disease states, when age, duration of clinic attendance, and use of anti-psychotic medications are taken into account. Our results show that patients receiving regular lithium treatment have a reduced prevalence of some neurological disorders and myocardial infarctions. One possible explanation of these results is that a protective effect of lithium observed in laboratory and animal studies may also be present in human patients receiving regular lithium therapy.

Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing.

Pregabalin is a new anxiolytic that acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha2-delta subunit of voltage-gated calcium channels. The current study evaluated the anxiolytic efficacy of BID versus TID dosing of pregabalin in patients with generalized anxiety disorder. Outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition generalized anxiety disorder and having baseline Hamilton Anxiety (HAM-A) total scores > or =20 were randomized to 6 weeks of double-blind treatment with pregabalin 200 mg/d (BID; N = 78), 400 mg/d (BID; N = 89), or 450 mg/d (TID; N = 88) or placebo (N = 86). Mean improvement in HAM-A total score at last observation carried forward end point was significantly greater on pregabalin 200 (P = 0.006), 400 (P = 0.001), and 450 mg/d (P = 0.005) compared with placebo. Pairwise comparisons of BID versus TID dosing found no difference in HAM-A change score at end point. All 3 pregabalin dosage groups showed significantly greater efficacy versus placebo at end point on the HAM-A psychic and somatic anxiety factor scores. Improvement on both factors was rapid: significance versus placebo was achieved as early as the first assessment at week 1, with > or =30% reduction in HAM-A severity and equal or greater improvement for every subsequent visit in > or =38% of patients in all 3 pregabalin dosage groups (P < or = 0.001). Pregabalin was well tolerated, and despite the fixed-dose study design, discontinuations caused by adverse events ranged from 9% to 13%--comparable with that observed with placebo (8%). This study demonstrates that pregabalin is an effective treatment of generalized anxiety disorder, with BID dosing showing similar efficacy and comparable tolerability with TID dosing.

Quality of life in patients with bipolar I depression: data from 920 patients.

OBJECTIVE: To determine the impact of acute depression on quality of life (QOL) in patients with bipolar I disorder and to compare these results with published data on QOL in patients with unipolar depression. METHODS: Quality of life was assessed using the SF-36 in bipolar patients (n = 958) who had recently experienced an episode of acute bipolar depression and participated in a large randomized, double-blind, safety and efficacy trial. Seven studies that included SF-36 data from patients with unipolar depression were identified in the published literature and descriptive comparisons of SF-36 scores were made between the unipolar depression trials and this bipolar depression trial. RESULTS: There were 920 patients who completed the SF-36. Mean transformed scores, which could range from 0 to 100, were very low in bipolar depressed patients for the role-physical (36.7), vitality (22.4), social functioning (29.9), role-emotion (11.4), and mental health (31.0) subscales. Mean SF-36 scores for all subscales were significantly and inversely correlated (p < 0.0001) with the HAM-D indicating that patients with milder depressive symptoms had better QOL. Further, the mean SF-36 scores for the bipolar sample were consistently lower compared with published data on QOL in unipolar depression on four of the eight subscales: general health; social functioning; role-physical, and role-emotional. CONCLUSIONS: While both unipolar and bipolar depression have serious detrimental effects on patient QOL, our results suggest that some aspects of QOL may be worse in bipolar depression.

Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study.

BACKGROUND: Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants. METHOD: Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study. RESULTS: One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants. CONCLUSION: Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy.