Antidepressant combinations: epidemiological considerations.

OBJECTIVE: To evaluate the treatment options in patients who do not respond appropriately to a single antidepressant alone. METHOD: The medical literature was reviewed. RESULTS: A number of strategies are available if a patient fails to respond adequately to initial antidepressant treatment, including the combination with another psychoactive drug. Evidence published to date appears to suggest that benzodiazepines are the drugs most frequently combined with antidepressants. The combination of two antidepressants together is less common, occurring in approximately 5-15% of cases showing a poor initial response. The key figures involved in such co-prescription are psychiatrists. CONCLUSION: There appears to be considerable variability in the data concerning combined prescription of antidepressants, with differences arising depending on the type of physician, the type of patient or illness and the geographical area. It is also unclear how closely research findings parallel with what doctors do in everyday practice.

Neuropharmacological basis of combining antidepressants.

OBJECTIVE: To review the neuropharmacological basis of antidepressant combination therapy. METHOD: Literature searches and other relevant material were obtained and reviewed. RESULTS: The overall clinical aim of combining antidepressants is to increase the efficacy whilst minimizing the side effects. Although such prescriptions are frequently based on the previous experience and knowledge, a sound neuropharmacological basis to support these combinations is desirable. When combining antidepressants, it is important to combine mechanisms of action, rather than simply one drug with another, and to aim for synergistic effects. The possibilities of combining mechanisms of action should also be exploited to the full if necessary, and the potential exists for combining two independent actions that have synergistic effects on the serotonergic, noradrenergic and even the dopaminergic systems. CONCLUSION: Unfortunately, there are still, as yet, insufficient data to categorically justify choosing one or other combination based only on the neuropharmacological evidence.

Combined antidepressants: clinical experience.

OBJECTIVE: To review the current literature on the use of combinations of antidepressive agents. METHOD: Literature searches were undertaken and reviewed on the use of combinations of antidepressants. RESULTS: Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine. CONCLUSION: Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.

Potentiation strategies for treatment-resistant depression.

OBJECTIVE: To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy. METHOD: Literature searches were undertaken and the results reviewed. RESULTS: Treatment-resistant depression is common (15-30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second-generation antipsychotics, psychostimulants, hormones and anticonvulsants. CONCLUSION: Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.

Use of antidepressant combinations: which, when and why? Results of a Spanish survey.

OBJECTIVE: The present study uses the data from a large survey conducted to examine the general practice of Spanish psychiatrists on the use of antidepressant combinations in the treatment of depressive disorders. METHOD: The sample was drawn from specialists and psychiatric residents practicing in Spain who were respondents to a questionnaire distributed during an annual national psychiatry meeting and sent by mail. RESULTS: A total of 1032 questionnaires were collected; following the data-filtering, 831 were analysed. Most psychiatrists (89%) believe that many patients do not respond to the first treatment; in such cases of non-response, 58% choose a combination of antidepressants as the next treatment option. Reasons for using the combined treatments include greater efficacy (57%), overcoming resistance to the first antidepressant (27%), faster onset of action (21%) and avoidance of side effects (17%). The most sought after pharmacological profile was serotonergic-noradrenergic (96%) and the most popular combinations were selective serotonin reuptake inhibitor (SSRI) + mirtazapine, SSRI + reboxetine and SSRI + tricyclic antidepressant. CONCLUSION: Antidepressant combinations are frequently used in clinical practice. Pharmacological profiles are always considered and SSRIs + mirtazapine is the option usually chosen.