Depression: Non-psychotheraputic therapies

It is widely agreed that two neurotransmitter systems are implicated in depression: serotonin (5HT) and norepinephrine (NE).  While many psychotherapeutic strategies have been adapted for the treatment of depression, the therapy of choice is the medication that makes existing serotonin more available by preventing its re-uptake, or the SSRI (Peterson, 2004). 

In depression, the brain networks become hyperactive, and the serotonin enhancing medication "calms down" the activity, helping the brain networks normalize and allowing a return to normal cognitive-affective functioning.  The SSRI medication helps reduce the dysfunction, or dysregulation, that causes depressive symptoms, especially uncontrollable worry (Peterson, 2004).

Sometimes there is no benefit from SSRI medication, and a common alternate strategy is non-SSRI medications such as bupropion, mirtazapine, or venlafaxine (Papakostas, 2008).  Mirtazapine and venlafaxine affect norepinephrine function (they are called noradrenergic) where norepinephrine is shown to reduce neuron excitability (Zhaoyang, 2009), and hence help keep the brain "calm" in ways achieved by SSRIs.

In the case of seasonal affective depression (SAD), a third medication, bupropion, is used to prevent the re-uptake of dopamine rather than serotonin (Modell, 2005).  SAD is a "hibernation-like response" typically triggered by the change of seasons that creates a desire, even craving, for sleep (Morano, 2003).  Bupropion is considered an "activating" medication (Rye, 1998) as it promotes the stimulating effects of dopamine.  Bupropion is also effective in treating the "sleepiness and fatigue" associated with major depression (Papakostas, 2008), which implies that there are widely differing seemingly contradictory types, or perhaps components, of depression requiring divergent treatment strategies.

Treatment resistant depression describes depression that won't respond effectively to medication.  While counselors remain a lifeline for the deeply depressed who cannot respond to treatment two electric stimulation therapies are used to stimulate the brain: electroconvulsive therapy and Deep brain stimulation (Bewernick, 2010).
 

References

Bewernick, B., Hurlemann, R., Matusch, A., Kayser, S., Grubert, C., Hadrysiewicz, B., et al. (2010). Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biological Psychiatry, 67(2), 110-116. doi:10.1016/j.biopsych.2009.09.013.

Modell, J., Rosenthal, N., Harriett, A., Krishen, A., Asgharian, A., Foster, V., et al. (2005). Seasonal affective disorder and its prevention by anticipatory treatment with Bupropion XL. Biological Psychiatry, 58(8), 658-667. doi:10.1016/j.biopsych.2005.07.021.

Morano, R. (2003). The sun also rises. Better Nutrition, 65(1), 46. Retrieved from Academic Search Premier database.

Papakostas, G., Fava, M., & Thase, M. (2008). Treatment of SSRI-resistant depression: A meta-analysis comparing within-versus across-class switches. Biological Psychiatry, 63(7), 699-704. doi:10.1016/j.biopsych.2007.08.010.

Petersen, T., Papakostas, G., Mahal, Y., Guyker, W., Beaumont, E., Alpert, J., et al. (2004). Psychosocial functioning in patients with treatment resistant depression. European Psychiatry, 19(4), 196-201. doi:10.1016/j.eurpsy.2003.11.006.

Rye, D., Dihenia, B., & Bliwise, D. (1998). Reversal of atypical depression, sleepiness, and REM-sleep propensity in narcolepsy with bupropion. Depression & Anxiety (1091-4269), 7(2), 92-95. Retrieved from Academic Search Premier database.

Zhaoyang, X., Pan-Yue, D., Rojanathammanee, L., Chuanxiu, Y., Grisanti, L., Permpoonputtana, K., et al. (2009). Noradrenergic depression of neuronal excitability in the entorhinal cortex via activation of TREK-2 K⁺ Channels. Journal of Biological Chemistry, 284(16), 10980-10991. doi:10.1074/jbc.M806760200.