Controversy exists about whether the newer antidepressants are as effective as the TCAs. Some meta-analyses,119-122 but not all,123 indicate that TCAs (eg, amitriptyline, clomipramine) and venlafaxine (at a dose of 150 mg or greater) are more effective than SSRIs (certainly citalopram, paroxetine) or moclobemide in severely depressed inpatients. Although this is not unanimously admitted, the efficacy of TCAs is related to the administered dose (a dose of 150 mg/day is more effective

than 75 mg/day in severe depression). However, owing to their anticholinergic adverse effects (such as dry mouth, constipation, blurred vision, impaired concentration, and confusion) TCAs are usually prescribed below recommended Inhibitors,research,lifescience,medical doses (for review see ref 4). Thus, in order to minimize

adverse effects, TCAs have to be started at a low dose and increased gradually (every 3 to 7 days); the delayed clinical response also makes it difficult to establish Inhibitors,research,lifescience,medical the optimal dose quickly (TCAs take 2 to 4 weeks before an antidepressant effect is evident). On the other hand, SSRIs and newer antidepressants are better tolerated than TCAs and are safer in overdose. Moreover, their dose formulation Inhibitors,research,lifescience,medical tends to ensure adequate dosing, and they can be administered at the recommended dose after a few days of obviously treatment at a lower dose. The adverse reactions associated with the SSRIs (eg, nausea, diarrhea, anxiety, agitation, sexual dysfunction, insomnia, and anorexia) may also occur with SNRIs. Some drugs have specific adverse effects, such as hypertension with venlafaxine and Inhibitors,research,lifescience,medical agranulocytosis with mianserin. It is noteworthy that mirtazapine, induce weight gain. New treatment options such as agomelatine will have to be taken into consideration, Inhibitors,research,lifescience,medical once available. Short-term outcome It is important to review patients regularly (usually weekly for the first 4 to 6 weeks) to monitor response,

compliance, side effects with treatment, and suicidal ideation. Adverse effects are often dose-dependent, and a dose reduction may Anacetrapib alleviate the problem. Moreover, tolerance occurs for many of the acute adverse effects of the antidepressants, probably as a result of receptor downregulation. For this reason, the dose can be gradually re-escalated, if needed for optimal efficacy, without the adverse effect necessarily recurring. If there is no response (< 25% improvement) after 3 weeks it is possible to increase the dose, while in case of a partial response, one could wait another 2 weeks before increasing the dose.124 What are the options in ease of nonresponse? When a patient does not respond to the first-choice antidepressant at an adequate dose, three strategies exist: increasing the dose of the antidepressant, switching to another antidepressant, or combining several drugs.