The chronic and recurrent nature of major depressive disorder is receiving increasing attention.
Approximately eight of ten people experiencing a major depressive episode will have at least one more episode during their lifetime, i.e. recurrent major depressive disorder.
In the 1990s, prolonged or lifelong pharmacotherapy emerged as the main therapeutic tool for preventing relapses of depression. This therapeutic approach is based on the effectiveness of antidepressant drugs compared with placebo in decreasing relapse risk and on the improved tolerability profile of the newer antidepressants compared with their older counterparts. However, outcome after discontinuation of antidepressant therapy does not seem to be affected by the duration of administration. Loss of clinical effects, despite adequate compliance, has also emerged as a vexing clinical problem.
The use of intermittent pharmacotherapy with follow-up visits is an alternative therapeutic option. This leaves patients with periods free of drugs and adverse effects and takes into account that a high proportion of patients would discontinue the antidepressant anyway. However, the problems of resistance (that a drug treatment may be associated with a diminished chance of response in subsequent treatments in those patients whose symptoms successfully responded to it but who discontinued it) and of discontinuation syndromes are substantial disadvantages of this therapeutic approach.
In recent years, several controlled trials have suggested that sequential use of pharmacotherapy in the treatment of the acute depressive episode and psychotherapy in its residual phase may improve long-term outcome. Patients, however, need to be motivated for psychotherapy, and skilled therapists have to be available.
Despite an impressive amount of research into the treatment of depression, there is still a paucity of studies addressing the specific problems that prevention of recurrent depression entails. It is important to discuss with the patient the various therapeutic options and to adapt strategies to the specific needs of patients.
This article was supported in part by a grant from the ‘Mental Health Evaluation Project’ (Istituto Superiore di Sanità, Rome, Italy) to Dr Fava and by grants from the Consiglio Nazionale delle Ricerche (CNR, Rome, Italy) and Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST, Rome, Italy) to Drs Fava and Sonino. The authors have no conflicts of interest to declare.
Ormel J, Oldehinkel T, Brilman E, et al. Outcome of depression and anxiety in primary care. Arch Gen Psychiatry 1993; 50: 759–76PubMedCrossRefGoogle Scholar
American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157 (Apr Suppl.): 1–45Google Scholar
Schulberg HC, Katon W, Simon GE, et al. Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry 1998; 55: 1121–7PubMedCrossRefGoogle Scholar
Hollon SD, Shelton RC. Treatment guidelines for major depressive disorder. Behav Ther 2001; 32: 235–58CrossRefGoogle Scholar
Baldessarini RJ. Drugs and the treatment of psychiatric disorders: antidepressant and antianxiety agents. In: Hardman JG, Limbird LE, Gilman AG, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill, 2001: 485–520Google Scholar
Kupfer DJ, Frank E, Perel JM, et al. Five-year outcome for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1992; 49: 769–73PubMedCrossRefGoogle Scholar
Thornton A, Lee P. Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol 2000; 53: 207–16PubMedCrossRefGoogle Scholar
Otto MW, Nierenberg AA. Assay sensitivity, failed trials, and the conduct of science. Psychother Psychosom 2002; 71: 241–3PubMedCrossRefGoogle Scholar
Dawson R, Lavori PW, Coryell WH, et al. Maintenance strategies for unipolar depression. J Affect Disord 1998; 49: 31–44PubMedCrossRefGoogle Scholar
Fava GA, Mangelli L, Ruini C. Assessment of psychological distress in the setting of medical disease. Psychother Psychosom 2001; 70: 171–5PubMedCrossRefGoogle Scholar
Mischoulon D, McColl-Vuolo F, Howarth S,et al. Management of major depression in the primary care setting. Psychother Psychosom 2001; 70: 103–7PubMedCrossRefGoogle Scholar
Viguera AC, Baldessarini RJ, Friedberg J. Discontinuing antidepressant treatment in major depression. Harv Rev Psychiatry 1998; 5: 293–306PubMedCrossRefGoogle Scholar
Byrne SE, Rothschild AJ. Loss of antidepressant efficacy during maintenance therapy. J Clin Psychiatry 1998; 59: 279–88PubMedCrossRefGoogle Scholar
Schmidt ME, Fava M, Zhang S, et al. Treatment approaches to major depressive disorder relapse. Part 1: dose increase. Psychother Psychosom 2002; 71: 190–4PubMedCrossRefGoogle Scholar
Frank E, Kupfer DJ, Perel JM, et al. Comparison of full dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression. J Affect Disord 1993; 27:139–45PubMedCrossRefGoogle Scholar
Davis JM, Janicak PG, Hogan DM. Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis. Acta Psychiatr Scand 1999; 100: 406–17PubMedCrossRefGoogle Scholar
Maj M, Pirozzi R, Kemali D. Long-term outcome of lithium prophylaxis in patients initially classified as complete responders. Psychopharmacology 1989; 98: 535–8PubMedCrossRefGoogle Scholar
Solomon DA, Keitner GI, Miller IW, et al. Course of illness and maintenance treatments for patients with bipolar disorder. J Clin Psychiatry 1995; 56: 5–13PubMedGoogle Scholar
Fava GA, Molnar G, Grandi S, et al. Prodromal symptoms and intermittent drug medication in mood disorders. Pharmacopsychiatry 1991; 24: 28–30PubMedCrossRefGoogle Scholar
Kupfer DJ, Frank E, Perel JM. The advantage of early treatment intervention in recurrent depression. Arch Gen Psychiatry 1989; 46: 771–5PubMedCrossRefGoogle Scholar
Streja DA, Hui RL, Streja E, et al. Selective contracting and patients outcomes. Am J Manag Care 1999; 5: 1133–42PubMedGoogle Scholar
Croghan TW, Lair TJ, Engelhart L, et al. Effect of antidepressant therapy on health care utilization and costs in primary care. Psychiatr Serv 1997; 48: 1420–6PubMedGoogle Scholar
Simon GE, Von Korff M, Heiligenstein JH, et al. Initial antidepressant choice in primary care. JAMA 1996; 275: 1897–902PubMedCrossRefGoogle Scholar
Dunn RL, Donoghue JM, Ozminkowski RJ, et al. Longitudinal patterns of antidepressant prescribing in primary care in the UK. J Psychopharmacol 1999; 13: 136–43PubMedCrossRefGoogle Scholar
Fava GA, Rafanelli C, Grandi S, et al. Six year outcome for cognitive behavioral treatment of residual symptoms in major depression. Am J Psychiatry 1998; 155: 1443–7PubMedGoogle Scholar
Fava M, Schmidt ME, Zhang S, et al. Treatment approaches to major depressive disorder relapse. Part II: re-initiation of antidepressant treatment. Psychother Psychosom 2002; 71: 155–99Google Scholar
Zajecka J, Tracy KA, Mitchell S. Discontinuation symptoms after treatment with serotonin reuptake inhibitors. J Clin Psychiatry 1997; 58: 291–7PubMedCrossRefGoogle Scholar
Fava GA, Ruini C. The sequential approach to relapse prevention in unipolar depression. World Psychiatry 2002; 1: 10–5PubMedGoogle Scholar
Fava GA, Rafanelli C, Grandi S, et al. Prevention of recurrent depression with cognitive behavioral therapy. Arch Gen Psychiatry 1998; 55: 816–20PubMedCrossRefGoogle Scholar
Blackburn IM, Moore RG. Controlled acute and follow-up trial of cognitive therapy in out-patients with recurrent depression. Br J Psychiatry 1997; 171: 328–34PubMedCrossRefGoogle Scholar
Paykel ES, Scott J, Teasdale JD, et al. Prevention of relapse in residual depression by cognitive therapy. Arch Gen Psychiatry 1999; 56: 829–35PubMedCrossRefGoogle Scholar
Teasdale JD, Segal ZV, Williams JMG, et al. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol 2000; 68: 615–23PubMedCrossRefGoogle Scholar
Jarrett RB, Kraft D, Doyle J, et al. Preventing recurrent depression using cognitive therapy with and without a continuation phase. Arch Gen Psychiatry 2001; 58: 381–8PubMedCrossRefGoogle Scholar
Jarrett RB, Kraft D, Schaffer M, et al. Reducing relapse in depressed out-patients with atypical features. Psychother Psychosom 2000; 69: 232–4PubMedCrossRefGoogle Scholar
Fava GA, Bartolucci G, Rafanelli C, et al. Cognitive behavioral management of patients with bipolar disorders relapsing while on lithium prophylaxis. J Clin Psychiatry 2001; 62: 556–9PubMedCrossRefGoogle Scholar
Fava GA, Ruini C, Rafanelli C, et al. Cognitive behavioral approach to loss of clinical effect during long-term antidepressant treatment. Am J Psychiatry 2002; 159: 2094–5PubMedCrossRefGoogle Scholar
Fava GA, Fabbri S, Sonino N. Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsycho-pharmacol Biol Psychiatry 2002; 26: 1019–27CrossRefGoogle Scholar
Faravelli C, Cosci F, Ciampelli M, et al. A self-controlled, naturalistic study of selective serotonin reuptake inhibitors versus tricyclic antidepressants. Psychother Psychosom 2003; 72: 95–101PubMedCrossRefGoogle Scholar
Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178: 234–41PubMedCrossRefGoogle Scholar
Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiat Clin N Am 1996; 19: 179–200CrossRefGoogle Scholar
Sonino N, Fava GA. CNS drugs in Cushing’s disease: pathophysiological and therapeutic implications for mood disorders. Prog Neuropsycopharmacol Biol Psychiatry 2002; 26: 1011–8CrossRefGoogle Scholar
Sonino N, Fava FA. Tolerance to antidepressant treatment may be overcome by ketoconazole. J Psychiatr Res 2003; 37: 171–3PubMedCrossRefGoogle Scholar
Morris MS, Fava M, Jacques PF, et al. Depression and folate status in the US population. Psychother Psychosom 2003; 72: 80–7PubMedCrossRefGoogle Scholar
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 3719-3030: global burden of disease study. Lancet 1997; 349: 1498–504PubMedCrossRefGoogle Scholar
Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–56PubMedCrossRefGoogle Scholar