Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis Tundo A, de Filippis R, De Crescenzo F. Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and metaanalysis Objective: Several depressed patients do not respond to traditional antidepressants. Our aim was to systematically review the effectiveness and safety of pramipexole in unipolar and bipolar depression. Methods: We conducted a systematic review of randomized clinical trials (RCTs) and observational studies on pramipexole for patients with major depressive episodes, following PRISMA guidelines. Our primary outcome measure was treatment response at endpoint. The study protocol was registered on PROSPERO: CRD42018108699. Results: We found five RCTs, three open-label trials and five observational studies, with 504 participants (57% women; mean age, 45.3 years; mean sample size, 39; median duration of treatment, 8 weeks; mean follow-up duration, 45 weeks; mean maximum dose, 1.62 mg). We found an overall short-term response rate of 52.2% and remission rate of 36.1%, and an overall long-term response rate of 62.1% and remission rate of 39.6%. In RCTs, patients treated with pramipexole had a superior response rate compared with placebo (RR: 1.77; 95% CI: 1.11-2.82) and similar to SSRIs (RR: 0.93; 95% CI: 0.44-1.95). Acceptability and tolerability were good, with nausea being the most frequent side-effect. Conclusion: Our study found some evidence for an effect of pramipexole for the treatment of major depressive episodes. Summations• Results from clinical trials found that pramipexole for major depressive episodes is superior to placebo and similar to SSRIs.• The use of pramipexole as antidepressant appears to be safe, with nausea being the most frequent side-effect.• Some side-effects commonly reported in studies on individuals with Parkinson's diseasesuch as lethargy, gambling, hypersexuality and compulsive shoppingare not reported for individuals treated with pramipexole for major depressive episodes. Limitations• Our systematic review includes only few studies.• The small sample size of the studies suggests that we are in an early phase of research and that a phase 3 trial is needed before drawing clinical conclusions.

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha(2)-delta subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150-450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the 'gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation.

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