Controversy exists over antidepressant use in bipolar II depression.

To compare the safety and effectiveness of antidepressant v. mood stabiliser monotherapy for bipolar type II major depressive episodes.

Randomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n = 65) v. lithium (n = 64) monotherapy in adult out-patients (trial registration number NCT00602537).

Primary outcome – venlafaxine produced a greater response rate (67.7%) v. lithium (34.4%, P<0.001). Secondary outcomes – venlafaxine produced a greater remission rate (58.5% v. 28.1%, P<0.001); greater decline in depression symptom scores over time (β=–5.32, s.e. = 1.16, χ2 = 21.19, P<0.001); greater reduction in global severity scores over time (β=–1.05, s.e. = 0.22, χ2 = 22.33, P<0.001); and greater improvement in global change scores (β=–1.31, s.e. = 0.32, χ2 = 16.95, P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments.

These findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium.

Depression can adversely affect employment status.

To examine whether there is a relative advantage of cognitive therapy or antidepressant medication in improving employment status following treatment, using data from a previously reported trial.

Random assignment to cognitive therapy (n = 48) or the selective serotonin reuptake inhibitor paroxetine (n = 93) for 4 months; treatment responders were followed for up to 24 months. Differential effects of treatment on employment status were examined.

At the end of 28 months, cognitive therapy led to higher rates of full-time employment (88.9%) than did antidepressant medication among treatment responders (70.8%), χ21 = 5.78, P = 0.02, odds ratio (OR) = 5.66, 95% CI 1.16–27.69. In the shorter-term, the main effect of treatment on employment status was not significant following acute treatment (χ21 = 1.74, P = 0.19, OR = 1.77, 95% CI 0.75–4.17); however, we observed a site×treatment interaction (χ21 = 6.87, P = 0.009) whereby cognitive therapy led to a higher rate of full-time employment at one site but not at the other.

Cognitive therapy may produce greater improvements in employment v. medication, particularly over the longer term.

Controversy exists over antidepressant use in rapid-cycling bipolar disorder.

Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder.

Randomised, double-blind, placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy (trial registration NCT0O044616).

The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups (P=0.20). The odds of relapse were similar between groups (P=0.36). The hazard of relapse was similar between groups (hazard ratio 0.87, 95% CI 0.40-1.91). Change in mania rating scores was similar between groups (P=0.86). There was no difference between groups in the rate of syndromal (P-0.27) or subsyndromal (P=0.82) hypomania.

Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term, relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder.

There is conflicting evidence about comorbid personality pathology in depression treatments.

To test the effects of antidepressant drugs and cognitive therapy in people with depression distinguished by the presence or absence of personality disorder.

Random assignment of 180 out-patients with depression to 16 weeks of antidepressant medication or cognitive therapy. Random assignment of medication responders to continued medication or placebo, and comparison with cognitive therapy responders over a 12-month period.

Personality disorder status led to differential response at 16 weeks; 66% v. 44% (antidepressants v. cognitive therapy respectively) for people with personality disorder, and 49% v. 70% (antidepressants v. cognitive therapy respectively) for people without personality disorder. For people with personality disorder, sustained response rates over the 12-month follow-up were nearly identical (38%) in the prior cognitive therapy and continuation-medication treatment arms. People with personality disorder withdrawn from medication evidenced the lowest sustained response rate (6%). Despite the poor response of people with personality disorder to cognitive therapy, nearly all those who did respond sustained their response.

Comorbid personality disorder was associated with differential initial response rates and sustained response rates for two well-validated treatments for depression.