Nonpharmacologic treatments

While the focus of treatment for depression is often on pharmacotherapy, the usefulness of nonpharmacologic treatment should not be forgotten.

Stimulation therapy: New therapies, such as vagal nerve stimulation and transcranial magnetic stimulation, are being developed. Both techniques are indicated by the FDA for use in depression. The magnitude of effect has varied from study to study. With further research, both forms of stimulation therapy show promise as future treatments for depression, especially in difficult-to-treat cases.91,92

Continue Reading

Exercise: No matter which treatment plan for depression you choose, encouraging exercise in healthy patients is a must given the benefits it will provide both mentally and physically. Exercise is simple, noninvasive, inexpensive, and effective in reducing symptoms of depression and has a low risk of side effects. However, exercise is almost always overlooked—sometimes by both the clinician and the patient. Exercise, which can be structured or home-based, has comparable effects to pharmacotherapy in reducing depression.93 Ernst investigated the theory that depression results from lack of synthesis of new neurons in the hippocampus.94 Studies in rats showed that exercise results in the synthesis of new neurons in the brain, much like that which is seen in the use of antidepressant therapy. Ernst concluded that exercise reduces depressive symptoms at a rate comparable to antidepressant therapy. The effects of exercise may not manifest as quickly as pharmacotherapy, but by 16 weeks, the groups had equivalent therapeutic benefit.95 Patients who continue with a regular exercise routine show lower rates of relapse compared with those who exercise only during a depressive episode.96

Psychotherapy: This treatment approach is potentially as effective as pharmacotherapy. Psychotherapy tends to yield better results in patients with mild-to-moderate depression than in those with severe depression.97 Several barriers to the usefulness of psychotherapy exist, including cost, convenience, and availability. Additionally, results vary significantly from person to person. Good candidates for psychotherapy include those who are experiencing their first episode of depression or whose depression is linked to a stressful life event. Additionally, persons who are interested in psychotherapy tend to have good results. Psychotherapy is effective monotherapy to reduce rates of relapse when used as continuation therapy.98


In choosing a treatment plan for depression, consideration of the unique features of your patient’s case is crucial. Individualizing treatment can lead to quicker recovery and improved quality of life, overall health, and well-being. A summary of treatments by symptom, subtype, and comorbidity appears in Table 2. Efficient management of depression will significantly reduce the morbidity and mortality associated with this widespread chronic illness.

Ms. Berns is a physician assistant at Family Medicine Specialists, P.C., in Cedar Rapids, Iowa. Special thanks to Don St. John, PA-C, department of psychiatry, University of Iowa Health Care, Iowa City, for his assistance on this article. The author has no relationships to disclose relating to the content of this article.


1. Conway MW, Miller MN. Mood disorders. In: Rakel RE, Bope ET, eds. Conn’s Current Therapy 2008. 60th ed. Philadelphia, Pa.: Saunders; 2008: chap 281.

2. St. John D. Depression. In: Moser RL. Primary Care for Physician Assistants: Clinical Practice Guidelines. 2nd ed. New York, N.Y.: McGraw-Hill Companies; 2001:Sect 16-5.

3. Kessler RC, Chiu WT, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. ArchGen Psychiatry. 2005;62: 617-627.

4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, D.C.: American Psychiatric Association; 1994.

5. Pignone MP, Gaynes BN, Rushton JL, et al. Screening for depression in adults. Summary of the evidence. Ann Intern Med. 2002;136:765-776.

6. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439-445.

7. Maletzky BM. The first-line use of electroconvulsive therapy in major affective disorders. J ECT. 2004;20: 112-117.

8. Perry P J. Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord. 1996;39:1-6.

9. Danish University Antidepressant Group. Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Psychopharmacology (Berl). 1986;90:131-138.

10. Bruijn JA, Moleman P, Mulder PG, van den Broek WW. Depressed in-patients respond differently to imiproamine and mirtazapine. Pharmacopsychiatry. 1999;32:87-92.

11. Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ; Comparative Efficacy Antidepressants Study Group. Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs. 2005;19:137-146.

12. Ribeiro L, Busnello JV, Kauer-Sant’Anna M, et al. Mirtazapine versus fluoxetine in the treatment of panic disorder. Braz J Med Biol Res. 2001;34:1303-1307.

13. Leinonen E, Skarstein J, Behnke K, et al. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. Int Clin Psychopharmacol. 1999;14:329-337.

14. Pae CU, Masand PS, Peindl K, et al. An open-label, rater-blinded, flexible-dose, 8-week trial of escitalopram in patients with major depressive disorder with atypical features. Prim Care Companion J Clin Psychiatry. 2008;10:205-210.

15. McGrath PJ, Stewart JW, Janal MN, et al. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry. 2000;157:344-350.

16. Pande AC, Birkett M, Fechner-Bates S, et al. Fluoxetine versus phenelzine in atypical depression. Biol Psychiatry. 1996;40:1017-1020.

17. Papakostas GI, Nutt DJ, Hallett LA, et al. Resolution of sleepiness and fatigue in major depressive disorder: a comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry. 2006;60:1350-1355.

18. Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2007;64:679-688.

19. Abraham G, Milev R, Stuart Lawson J. T3 augmentation of SSRI resistant depression. J Affect Disord. 2006;91: 211-215.

20. Iosifescu DV, Nierenberg AA, Mischoulon D, et al. An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry. 2005;66:1038-1042.

21. DeBatistta C, Doghramji K, Menza MA, et al; Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry. 2003;64:1057-1064.

22. Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry. 2005;66:85-93.

23. Thase ME, Fava M, DeBattista C, et al. Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study. CNS Spectr. 2006;11:93-102.

24. Michelson D, Adler LA, Amsterdam JD, et al. Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68:582-587.

25. McElroy SL, Guerdijikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiatry. 2007;68:390-398.

26. Lam RW, Levitt AJ, Levitan, RD, et al. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Am J Psychiatry. 2006;163:805-812.

27. Westrin A, Lam RW. Seasonal affective disorder: a clinical update. Ann Clin Psychiatry. 2007;19:239-246.

28. Ruhrmann S, Kasper S, Hawellek B, et al. Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder. Psychol Med. 1998;28:923-933.

29. Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005;162: 656-662.

30. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;(2):CD004050.

31. Gjerdingen D. The effectiveness of various postpartum depression treatments and the impact of antidepressant drugs on nursing infants. J Am Board Fam Pract. 2003;16:372-382.

32. Shah NR, Jones JB, Aperi J, et al. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis. Obstet Gynecol. 2008;111:1175-1182.

33. Steiner M, Ravindran AV, LeMelledo JM, et al. Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women. J Clin Psychiatry. 2008;69:991-998.

34. Erikkson E, Ekman A, Sinclair S, et al.  Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder. J Clin Psychopharmacol. 2008;28:195-202.

35. Freeman EW, Rickels K, Sondheimer SJ, Polansky M. Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial. Arch Gen Psychiatry. 1999;56:932-939.

36. Joffe H, Petrillo LF, Viguera AC, et al. Treatment of premenstrual worsening of depression with adjunctive oral contraceptive pills: a preliminary report. J Clin Psychiatry. 2007;68:1954-1962.

37. Grigoriadis S, Kennedy SH. Role of estrogen in the treatment of depression. Am J Ther. 2002;9:503-509.

38. Fountoulakis KN, Vieta E. Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. Int J Neuropsychopharmacol. 2008;11:999-1029.

39. Bowden C, Göğüs A, Grunze, H, et al. A 12-week, open, randomized trial comparing sodium valproate to lithium in patients with bipolar I disorder suffering from a manic episode. Int Clin Psychopharmacol. 2008;23:254-262.

40. Weisler RH, Kalali AH, Ketter TA; SPD417 Study Group. A mulitcenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry. 2004;65:478-484.

41. Tohen M, Bowden CL, Smulevich AB, et al. Olanzapine plus carbamaz­epine v. carbamazepine alone in treating manic episodes. Br J Psychiatry. 2008;192:135-143.

42. Vieta E, Cruz N, Garcia-Campayo J, et al. A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder. Int J Neuropsychopharmacol. 2008;11:445-452.

43. Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163:232-239.

44. Post RM, Altshuler LL, Leverich GS, et al. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion, and sertraline. Br J Psychiatry. 2006;189:124-131.

45. Atamaca M, Kuloglu M, Tezcan E, Unal A. Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Hum Psychopharmacol. 2002;17:401-405.

46. Versiani M. A review of 19 double-blind placebo-controlled studies in social anxiety disorder (social phobia). World J Biol Psychiatry. 2000;1:27-33.

47. Muller JE, Koen L, Seedat S, Stein DJ. Social anxiety disorder: current treatment recommendations. CNS Drugs. 2005;19:377-391.

48. Muehlbacher M, Nickel MK, Nickel C, et al. Mirtazapine treatment of social phobia in women: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2005;25:580-583.

49. Schatzberg AF, Kremer C, Rodrigues HE, Murphy GM Jr; Mirtazapine vs. Paroxetine Study Group. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry. 2002;10:541-550.