Efficacy

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Table 15.2 summarizes the drugs of the SSRI and SNRI families that have been found to be effective in the treatment of primary depressive disorders, and the recommended starting and maximal doses. From the stand-point of efficacy, the choice of SSRI or SNRI must depend on whether the patient has only a depressive episode or a mixed depression/anxiety (and/or panic) disorder. Furthermore, the elimination of co-morbid anxiety symptoms with a depressive disorder is as important as that of symptoms of depression, as the former have been associated with an increased suicidal risk [30].

Given comparable efficacy among SSRIs and SNRIs, the lack of pharmacokinetic interactions with AEDs and better tolerance, we recommend the use of escitalopram or citalopram first and sertraline as an alternative. If patients have already undergone a trial with an SSRI at optimal doses, clinicians should consider using an SNRI as the next option. In fact, recent studies have suggested that the use of SNRIs can yield symptom remission in patients in whom an SSRI had failed to do so. The suggested advantage of SNRIs is thought to be based on its dual effect on serotonin and norepinephrine neurotransmitters (and at higher doses, on dopaminergic transmission) in contrast to the effect of SSRIs on serotonin alone. It should be noted, however, that venlafaxine yields a noradrenergic effect at moderately high doses, but not at low doses. Such is not the case of the new SNRI duloxetine hydrochloride, which yields noradrenergic effects at lower doses as well as mirtazapine. However, the safety of the latter two drugs in PWE is yet to be established.

There are also data suggesting that SNRIs may be more effective in patients with physical symptoms (pains and aches), fatigue and psychomotor slowing, which can be relatively common complaints in depressed patients. Since a successful treatment of any depressive disorder is one that yields complete symptom remission, eradication of these physical symptoms should be always considered, as residual symptoms are associated with a higher risk of recurrence of major depression.

One cautionary note is in order, however: the therapeutic effect of SSRIs and SNRIs may be identified 3-6 weeks after starting the drug. As SSRIs can, at times, cause restlessness and mild anxiety at the start of therapy, a short course of a benzodiazepine such as clonazepam (0.5-1 mg/day) should be considered in patients with co-morbid anxiety and depression. Also, discontinuation of TCAs, SSRIs and SNRIs has to be carried out gradually through a tapering schedule to avert the development of discontinuation emergent symptoms. These include somatic symptoms such as nausea, vomiting, tremors, diaphoresis, ataxia, movement disorders and sleep disturbances. SSRIs and SNRIs with the shorter half-lives are associated with a higher risk of developing these symptoms.

In patients in need of a prompt anxiolytic and sedative effect, the a2-antagonist mirtazapine may be a good option. The anti-depressant effect of the drug takes up to 4-6 weeks to become apparent, however. Weight gain is a potential problem with this drug and should be closely monitored.

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