Augmentation Strategies in Resistant Depression - Some Are Effective and Well Tolerated

Drug Ther Perspect. 2001;17(5) 

In This Article

Pindolol Speeds up Response

Several controlled studies have shown that the addition of pindolol to SSRI therapy rapidly potentiates the effects of these antidepressants.[1,2] While more rapid improvement was shown with the combination, most studies found no advantage at the end of the study period.[2] Pindolol plus SSRIs appear to be well tolerated.[1] Only a small number of patients withdrew from studies of pindolol plus paroxetine or fluoxetine because of adverse events.[12,13] The most common adverse events included nausea, diarrhoea and headache.[12] Empirical evidence lacking for other strategies The efficacy and tolerability of augmentation strategies with valproic acid (sodium valproate), carbamazepine, psychostimulants and buspirone are based on case reports and nonblind studies rather than controlled trials. In general, beneficial effects have been reported with augmentation regimens involving drugs presented in the table. However, carbamazepine (an enzyme inducer) or valproic acid (an enzyme inhibitor) should be used with caution with TCAs because of the risk of decreases or increases in plasma TCA concentrations.

Carbamazepine may also increase concentrations of hydroxy-tricyclic antidepressant metabolites and thus may be cardiotoxic. It should also be noted that stimulants may increase blood concentrations of other drugs and the risk of hypertensive crises when administered in combination with MAOIs. In addition, their adverse effects, abuse and dependence potential and the risks of withdrawal reactions need to be considered particularly when being used with antidepressants. Buspirone is a partial serotonin 5-HT1A-receptor agonist and may enhance serotonin transmission when given with an SSRI, thus potentiating SSRI-associated adverse effects such as apathy or sexual dysfunction.[1]