Lifetime prevalence of MDD is 16.2% but most patients are not adequately treated. SSRIs demonstrate equal efficacy with older drugs but are better tolerated and accepted. 

NSRIs are slightly more efficacious 63% vs 59% for traditional SSRIS. 

The more severe the depressive symptoms, the more robust the response.

Review of several studies report a DECREASE in the rate of suicide and ideation with prescriptions of antidepressants.  The studies where depression was not the only diagnosis but included use of antidepressants for other clinical indications may show   higher rates. 

Studies show a true antidepressant reponse can occur within the first 1-2 weeks of treatment. 75% of patients respond by week 4. 

Factors predictive of risk of relapse: prior episode, more severely ill, and the  presence of residual symptoms.

TRD treatment strategies: switching to another medication.  25%,  Switching to a third medication 14%, and switching to another class demonstrate and additonal  13% improved. 

Augmentation strategies: add mirtazapine- (45%), bupropion (30%), buspirone, atypical antipsychotics, lithium, lamictal, T3, or SAMe. The most research has been with atypicals, lithium, and thyroid augmentation. 

Other possible treatments include :  Agomelatine- a melatonin receptor agonist and a 5-HT2c antagonist, and Glutamatergic agents. 

Glutamatergic agents: NMDA receptor antagonists – include memantine and ketamine. Riluzole-currently treats ALS and acts to increase  release of glutamate and block reuptake-with some additional promise in treating TRD. 

Pramipexole- pre-synaptic dopamine agonist. 

Modafinil-good for depression related fatigue and sleepiness.