Again, despite the availability of a range of medications for

SAD, many patients either do not respond or remit.129 Thus, there is an ongoing need for further work on treatment-refractory cases and novel treatment targets. Early on the MAOIs showed efficacy for SAD in a number of placebo-controlled trials.130 In particular, phenelzine, an irreversible MAOI, was efficacious.131-133 However, as noted earlier, this class of agent requires dietary restrictions and is associated with a range of potential adverse somehow events. The newer reversible MAOIs (RIMAs), such as moclobemide Inhibitors,research,lifescience,medical and brofaromine, do not require such dietary restrictions and are well tolerated. However, they have not proved consistently efficacious in SAD130,134; thus although they are part of the current armamentarium, they are not Imatinib Mesylate typically considered first-line agents.8,9,11,135 The benzodiazepine clonazepam showed promise in the short-

and long-term treatment of patients with Inhibitors,research,lifescience,medical SAD.136,137 However, once again, given risk:benefit considerations, benzodiazepines are not usually recommended as first-line agents for SAD.8,9,11,135 Several SSRIs have been shown to be efficacious and relatively well-tolerated in the treatment of SAD.138,130,139 Both paroxetine and sertraline are FDA-approved Inhibitors,research,lifescience,medical for treatment of this disorder (Table IV). Given the substantial evidence base indicating the efficacy and safety of SSRIs, they are typically recommended as the firstline pharmacotherapy in treatment guidelines.8,9,11,135 Table IV. Select meta-analyses in seasonal affective Inhibitors,research,lifescience,medical disorder treatment. SSRI, selective serotonin reuptake inhibitor, MAOI, monoamine oxidase inhibitor Of the SNRIs, venlafaxine is the best studied in SAD, where it has shown efficacy in a number of RCTs.134

This agent is therefore considered a reasonable alternative to the use of SSRIs in a number of treatment guidelines, and is FDA-approved for such use.8,9,11,135 Current guidelines recommend that active treatment with SSRIs/SNRIs Inhibitors,research,lifescience,medical should be continued for at least a year.8,9,11 This recommendation is supported by a number of placebo-controlled relapse-prevention studies.139 Several anticonvulsant agents have also been studied in SAD.134,140,141 Both gabapentin88 and pregabalin, for example, have shown efficacy compared with placebo. However, neither agent is AV-951 registered for the treatment of SAD, and additional studies are required before their routine use can be recommended. A limited number of studies have investigated atypical antipsychotics in SAD.142 A consideration of risk:benefit ratio suggests that these agents should not yet be viewed as a first-line option in SAD.135 However, their role as an augmenting strategy in treatment-refractory cases perhaps deserves additional consideration. Up to 50% of SAD patients do not respond to initial pharmacological treatment.