Skip to main content Accessibility help

Pharmacotherapy of Seasonal Affective Disorder

  • Edda Pjrek, Dietmar Winkler and Siegfried Kasper


Seasonal affective disorder is a common variant of recurrent major depressive disorder or bipolar disorder. Treatment with bright artificial light has been found to be effective in this condition. However, for patients who do not respond to light therapy or those who lack compliance, conventional drug treatment with antidepressants also has been proposed. Substances with selective serotonergic or noradrenergic mechanisms should be preferred over older antidepressants. Although there are a number of open and controlled studies evaluating different compounds, these studies were often limited by relatively small sample sizes. Furthermore, there are no studies specifically addressing bipolar seasonal depression. This article will review the published literature on pharmacotherapy of seasonal affective disorder.


Corresponding author

Please direct all correspondence to: Edda Pjrek, MD, Department of General Psychiatry, Medical University of Vienna, Währinger Gürtel 18-0-1090 Vienna, Austria; Tel: 43-1-40400-3568, Fax: 43-1-40400-3099; E-mail:


Hide All
1.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. text rev, Washington, DC: American Psychiatric Association; 2000.
2.Winkler, D, Praschak-Rieder, N, Willeit, M, et al.Seasonal affective depression in 2 German speaking university centers: Bonn, Vienna. Clinical and demographic characteristics [German]. Nervenarzt. 2002;73:637643.
3.Mersch, PP, Middendorp, HM, Bouhuys, AL, Beersma, DG, van den Hoofdakker, RH. Seasonal affective disorder and latitude: a review of the literature. J Affect Disord. 1999;53:3548.
4.Blazer, DG, Kessler, RC, Swartz, MS. Epidemiology of recurrent major and minor depression with a seasonal pattern. The National Comorbidity Survey. Br J Psychiatry. 1998;172:164167.
5.Kasper, S, Wehr, TA, Bartko, JJ, Gaist, PA, Rosenthal, NE. Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland. Arch Gen Psychiatry. 1989;46:823833.
6.Levitt, AJ, Boyle, MH, Joffe, RT, Baumal, Z. Estimated prevalence of the seasonal subtype of major depression in a Canadian community sample. Can J Psychiatry. 2000;45:650654.
7.Terman, M, Terman, JS, Quitkin, FM, McGrath, PJ, Stewart, JW, Rafferty, B. Light therapy for seasonal affective disorder: a review of efficacy. Neuropsychopharmacology. 1989;2:122.
8.Winkler, D, Pjrek, E, Konstantinidis, A, Stastny, J, Kasper, S. Seasonal affective disorder—pathophysiology and clinical management. Acta Psychiatr Belg. In press.
9.Terman, JS, Terman, M, Lo, ES, Cooper, TB. Circadian time of morning light administration and therapeutic response in winter depression. Arch Gen Psychiatry. 2001;58:6975.
10.Jacobsen, FM, Murphy, DL, Rosenthal, NE. The role of serotonin in seasonal affective disorder and the antidepressant response to phototherapy. In: Rosenthal, NE, Blehar, MC, eds. Seasonal Affective Disorder and Phototherapy. New York, NY: Guilford Press; 1989:333341.
11.Dilsaver, SC, Jaeckle, RS. Winter depression responds to an open trial of tranylcypromine. J Clin Psychiatry 1990;51:326329.
12.Dilsaver, SC, Del Medico, VJ, Quadri, A, Jaeckle, S. Pharmacological responsiveness of winter depression. Psychopharmacol Bull. 1990;26:303309.
13.Teicher, MH, Glod, CA. Seasonal affective disorder: rapid resolution by low-dose alprazolam. Psychopharmacol Bull. 1990;26:197202.
14.Lingjaerde, O, Haggag, A. Moclobemide in winter depression: some preliminary results from an open trial. Nord J Psychiatry. 1992;46:201203.
15.Wirz-Justice, A, van der Velde, P, Bucher, A, Nil, R. Comparison of light treatment with citalopram in winter depression: a longitudinal single case study. Int Clin Psychopharmacol. 1992;7:109116.
16.Hesselmann, B, Habeler, A, Praschak Rieder, N, Willeit, M, Neumeister, A, Kasper, S. Mirtazapine in seasonal affective disorder (SAD): a preliminary report. Human Psychopharmacology Clinical and Experimental. 1999;14:5962.
17.Hilger, E, Willeit, M, Praschak-Rieder, N, Stastny, J, Neumeister, A, Kasper, S. Reboxetine in seasonal affective disorder: an open trial. Eur Neuropsychopharmacol. 2001;11:15.
18.Martinez, B, Kasper, S, Ruhrmann, S, Moller, HJ. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol. 1994;7(suppl 1):S29S33.
19.Partonen, T, Lönnqvist, J. Moclobemide and fluoxetine in treatment of seasonal affective disorder. J Affect Disord. 1996;41:9399.
20.Ruhrmann, S, Kasper, S, Hawellek, B, et al.Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder. Psychol Med. 1998;28:923933.
21.Pjrek, E, Winkler, D, Stastny, J, Konstantinidis, A, Heiden, A, Kasper, S. Bright light therapy in seasonal affective disorder—does it suffice? Eur Neuropsychopharmacol. 2004;14:347351.
22.Neumeister, A, Praschak-Rieder, N, Besselmann, B, Rao, ML, Gluck, J, Kasper, S. Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy. Arch Gen Psychiatry. 1997;54:133138.
23.Schwatz, PJ, Murphy, DL, Wehr, TA, et al.Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms. Arch Gen Psychiatry. 1997;54:375385.
24.Willeit, M, Praschak-Rieder, N, Neumeister, A, et al.[1231]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry. 2000;47:482489.
25.Wurtman, JJ. Depression and weight gain: the serotonin connection. J Affect Disord. 1993;29:183192.
26.McGrath, RE, Buckwald, B, Resnick, EVThe effect of L-tryptophan on seasonal affective disorder. J Clin Psychiatry. 1990;51:162163.
27.O'Rourke, D, Wurtman, JJ, Wurtman, RJ, Chebli, R, Gleason, R. Treatment of seasonal depression with d-fenfluramine. J Clin Psychiatry. 1989;50:343347.
28.Turner, EH, Schwartz, PJ, Lowe, CH, et al.Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder. J Clin Psychopharmacol. 2002;22:216220.
29.Lam, RW, Gorman, CP, Michalon, M, et al.Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry. 1995;152:17651770.
30Rosenthal, NE, Jacobsen, FM, Sack, DA, et al.Atenolol in seasonal affective disorder: a test of the melatonin hypothesis. Am J Psychiatry. 1988;145:5256.
31.Lingjaerde, O, Reichbom-Kjennerud, T, Haggag, A, Gartner, I, Narud, K, Berg, EM. Treatment of winter depression in Norway. II. A comparison of the selective monoamine oxidase A inhibitor moclobemide and placebo. Acta Psychiatr Scand. 1993;88:372380.
32.Oren, DA, Moul, DE, Schwartz, PJ, Wehr, TA, Rosenthal, NE. A controlled trial of levodopa plus carbidopa in the treatment of winter seasonal affective disorder: a test of the dopamine hypothesis. J Clin Psychopharmacol. 1994;14:196200.
33.Oren, DA, Teicher, MH, Schwartz, PJ, et al.A controlled trial of cyanocobalamin (vitamin B12) in the treatment of winter seasonal affective disorder. J Affect Disord. 1994;32:197200.
34.Schlager, DS. Early-morning administration of short-acting beta blockers for treatment of winter depression. Am J Psychiatry. 1994;151:13831385.
35.Leppamaki, S, Partonen, T, Vakkuri, O, Lonnqvist, J, Partinen, M, Laudon, M. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. Eur Neuropsychopharmacol. 2003;13:137145.
36.Martiny, K, Lunde, M, Simonsen, C, et al.Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo-controlled study. Acta Psychiatr Scand. 2004;109:230234.
37.Moscovitch, A, Blashko, CA, Eagles, JM, et al.A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Psychopharmacology (Berl). 2004;171:390397.
38.Modell, JG, Rosenthal, NE. Once-daily bupropion XL for the prevention of seasonal major depressive episodes. Neuropsychopharmacology. 2004;29(suppl 1):S157.
39.Neumeister, A, Turner, EH, Matthews, JR, et al.Effects of tryptophan depletion vs catecholamine depletion in patients with seasonal affective disorder in remission with light therapy. Arch Gen Psychiatry. 1998;55:524530.
40.Dilsaver, SC, Qamar, AB, Del Medico, VJ. The efficacy of bupropion in winter depression: results of an open trial. J Clin Psychiatry. 1992;53:252255.
41.Ascher, JA, Cole, JO, Colin, JN, et al.Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995;56:395401.
42.Lundt, L. Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study. J Affect Disord. 2004;81:173178.
43.Wisor, JP, Eriksson, KS. Dopaminergic-adrenergic interactions in the wake promoting mechanism of modafinil. Neuroscience. 2005;132:10271034.
44.Winkler, D, Willeit, M, Praschak-Rieder, N, et al.Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample. Eur Arch Psychiatry Clin Neurosci. 2002;252:5462.
45.Williams, JB, Link, MJ, Rosenthal, NE, Amira, L, Terman, M. Structured Interview Guide for the Hamilton Rating Scale—Seasonal Affective Disorder Version (SIGH-SAD; SIGH-SAD-SR, self-rating version). New York, NY: New York State Psychiatric Institute; 1992.
46.Yamadera, H, Okawa, M, Takahashi, K. Open study of effects of alprazolam on seasonal affective disorder. Psychiatry Clin Neurosci. 2001;55:2730.
47.Paterson, AM, Foldes, A. Melatonin and farm animals: endogenous rhythms and exogenous applications. J Pineal Res. 1994;16:167177.
48.Dahl, K, Avery, DH, Lewy, AJ, et al.Dim light melatonin onset and circadian temperature during a constant routine in hypersomnic winter depression. Acta Psychiatr Scand. 1993;88:6066.
49.Stoschitzky, K, Sakotnik, A, Lercher, P, et al.Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55:111115.
50.Cruickshank, JM, Neil-Dwyer, G, Cameron, MM, McAinsh, J. Beta-Adrenoreceptor-blocking agents and the blood-brain barrier. Clin Sci (Lond). 1980;59(suppl 6):453s455s.
51.Millan, MJ, Gobert, A, Lejeune, F, et al.The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther. 2003;306:954964.
52.Millan, MJ, Brocco, M, Gobert, A, Dekeyne, A. Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl). 2005;77:448458.
53.Bourin, M, Mocaer, E, Porsolt, R. Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci. 2004;29:126133.
54.Hintikka, J, Tolmunen, T, Tanskanen, A, Viinamaki, H. High vitamin B12 level and good treatment outcome may be associated in major depressive disorder. BMC Psychiatry. 2003;3:17.
55.Ikeda, M, Honda, K, Inoue, S. Vitamin B12 amplifies circadian phase shifts induced by a light pulse in rats. Experientia. 1996;52:691694.
56.Mayer, G, Kroger, M, Meier-Ewert, K. Effects of vitamin B12 on performance and circadian rhythm in normal subjects. Neuropsychopharmacology. 1996;15:456464.
57.Gloth, FM 3rd, Alam, W, Hollis, B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3:57.
58.Labbate, LA, Lafer, B, Thibault, A, Sachs, GS. Side effects induced by bright light treatment for seasonal affective disorder. J Clin Psychiatry. 1994;55:189191.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed