Previous studies have demonstrated that night-shift work is associated with adverse effects impacting physical and psychological health, including the Shift Work Disorder (SWD). SWD is a circadian rhythm disorder characterized by sleepiness and insomnia, resulting from working a shift other than the traditional daytime-shift. Armodafinil, a modafinil longer-lasting R-isomer, is approved for SWD treatment. Due to its pharmacodynamic profile, it may result in more sustained wakefulness during night-shifts than Modafinil.

To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of Armodafinil vs Modafinil and/or placebo on reducing SWD excessive sleepiness.

Will follow PRISMA guidelines. A systematic search will be conducted on PubMed, Web of Science, Scopus and ClinicalTrials.gov databases. RCTs comparing Armodafinil with Modafinil and/or Placebo for SWD treatment will be included. No language nor date restrictions will be applied. Outcomes of interest are prespecified as follows: the primary endpoint will be objective sleepiness; secondary endpoints will include subjective sleepiness, adverse effects, awareness, reaction time, memory and cognition. Retrieved studies will be independently screened for eligibility by two reviewers. Disagreements will be solved by consensus or by a third reviewer. Primary studies methodological quality will be assessed and data extracted independently using a standardized extraction-form.

Data will be described and reported as narrative text and summary tables. Heterogeneity of the included studies will be assessed and, if possible, a meta-analysis will be conducted.

It is expected that this systematic review and meta-analysis favours Armodafinil over Modafinil and placebo in the treatment of SWD.

No significant relationships.

Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work aims to explore the role of add-on stimulant and stimulant-like medication in resistant bipolar depression patients.

Systematic review of add-on stimulants and stimulant-like drugs in resistant bipolar depression by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analysis was performed using the random-effects models. Heterogeneity was evaluated with Cochran’s Q and I2 statistics.

Six randomized controlled trials of add-on modafinil, armodafinil, and lisdexamphetamine (LDX) (n = 813) vs placebo (n = 815) in the treatment of resistant bipolar depression were included. These drugs were more likely to induce remission from an episode of resistant bipolar depression (relative risk [RR] = 1.37; 95% confidence interval [CI]: 1.06-1.77; number needed to treat for an additional beneficial outcome = 16). Moreover, they did not induce more dropouts than placebo (RR = 1.04; 95% CI: 0.91-1.18), nor did they increase the risk of adverse effects (53/772 vs 41/771) at the end of treatment (RR = 1.30; 95% CI: 0.81-2.10; number needed to treat for an additional harmful outcome = 62). Suicidality and manic switch were not affected by active treatment. Heterogeneity was low (Cochran’s Q: P > .05), but sometimes with a large CI.

LDX, modafinil, and armodafinil seem to offer a reasonably well-tolerated and safe treatment in resistant bipolar depression. Treatment guidelines should, therefore, be revised to include these medications earlier in the therapeutic algorithm for resistant acute bipolar depression. Further research is, however, necessary for the elucidation of the clinical usefulness of these and other similar compounds.

Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression.

A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality.

Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine-fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational.

Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression.