Consultant.
No. 9
Depression:
Guidelines for Effective Primary Care, Part 2, Treatment
By HANI RAOUL KHOUZAM, MD, MPH |
August 1, 2007
University of California, San Francisco
Dr Khouzam is associate clinical professor of psychiatry at University of California, San Francisco Medical School, Fresno Medical Education Program; clinical instructor in medicine at Harvard Medical School in Boston; and former visiting lecturer in the department of psychiatry and behavioral sciences at the University of Oklahoma College of Medicine in Oklahoma City. He is also staff psychiatrist, medical director, and interim chief of the chemical dependency treatment program in the Veterans Affairs Central California Health Care System in Fresno.
St John's wort (Hypericum perforatum). This herb is widely used in Europe for the treatment of depression. It is available over-the-counter in many pharmacies and health food stores in the United States. Although it may have some merit in treating mild to moderate depression of limited duration, it is not recommended for major depression.27 It appears to have multiple actions, including inhibition of MAO and inhibition of 5-HT uptake.
Many drugs interact with St John's wort. It can increase the metabolization of some drugs, including oral contraceptives and protease inhibitors, thus reducing their effects. Because it also decreases the effects of cyclosporine, rejection of transplanted organs can occur. St John's wort also increases sensitivity to sunlight. Studies are under way about its place in the armamentarium.
SAM-e. The production of SAM-e is impaired in persons who are depressed.1 It has been hypothesized that supplementation with SAM-e increases levels of 5-HT, DA, and phosphatides, and enhances 5-HT- and DA-receptor site binding, thus leading to amelioration of depression. SAM-e breaks down into homocysteine, elevated levels of which have been correlated with heart disease.28
Omega-3 fatty acid. Although it has been reported to alleviate depression, omega-3 fatty acid may exert a dose-related effect on bleeding time.27 Careful ongoing monitoring of bleeding time may be necessary if this supplement is used to treat depression.
APPROACHES FOR TREATMENT-RESISTANT DEPRESSION
Augmentation and combination therapy. The addition of another agent such as lithium, thyroid hormone, a stimulant, or another antidepressant may be helpful for a patient with refractory depression.6 Augmentation with an atypical antipsychotic medication may also be useful.29 When major depression has psychotic features, the combination of an antipsychotic with an antidepressant may be an appropriate initial strategy; however, some clinicians prefer to treat the psychosis first before adding an antidepressant.30
Electroconvulsive therapy (ECT). If aggressive pharmacological interventions are not effective, consider ECT. To reduce the cognitive side effects of ECT, various strategies have been used31:
- Widely spaced treatments, with only one seizure per session.
- Unilateral nondominant placement of electrodes.
- Brief-pulse rather than sine-wave stimulus wave forms.
- Decreased dose of electricity.
- Tailored doses of anesthetic before treatment.
- Avoidance of concomitant psychotropic medication.
More recently, repetitive transcranial stimulation and vagal nerve stimulation have been tested and appear to be somewhat effective.32
Surgery. Psychosurgical interventions, including MRI-guided ste- reotactic cingulotomy, have been successful in some treatment-resistant patients.33
Light therapy. Patients with seasonal affective disorder can be treated with exposure to bright light (at least 2500 lux), preferably in the morning. Some patients may also respond to lithium and antidepressants.33
Treatment of medical conditions. Medical complaints that are not adequately addressed worsen depression and complicate treatment. Pain is one of the most frequently reported and bothersome physical symptoms.23 Even in the absence of depression, antidepressants have been shown to play a role in the treatment of pain.
Both 5-HT and NE are important modulators of pain sensations. TCAs with dual mechanisms of action, such as amitriptyline, are effective in controlling chronic pain, whereas SSRIs have more modest effects.23 Dual-action agents, such as venlafaxine, may be more effective in the relief of pain and have fewer adverse effects than TCAs.19 Duloxetine has also been shown to reduce overall pain severity in depressed patients, compared with placebo.20 This reduction in pain occurred more rapidly than the antidepressant effect, which suggests that there may be a different mechanism of action for pain relief.
PROGNOSIS
Depression is often chronic, with alternating relapses and remissions. About one third of patients with a single episode of major depression will have another episode within 1 year after discontinuing treatment, and more than half will have a recurrence during their lifetimes.25 Greater severity of depression, persistence of symptoms, and a higher number of previous episodes are the best predictors of recurrence.6 Chronic depression frequently develops in patients with multiple recurrences and in those with comorbid medical and psychiatric conditions.6
EVIDENCED-BASED MEDICINE:
•McIntyre RS, Konarski JZ, Soczynska JK, Kennedy SH. Residual anxiety symptoms in depressed primary care patients. J Psychiatr Pract. 2007;13:125-128.
•Sorensen J, Stage KB, Damsbo N, et al. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care. Nord J Psychiatry. 2007;61:100-108.
GUIDELINES:
•Depression in Primary Care: Detection, Diagnosis, and Treatment. Clinical practice guideline no. 5. Rockville, Md: US Department of Health and
Human Services, Public Health Services, Agency for Health Care Research and Quality; 1993. AHRQ publication 93-0551.
•Depression: Guidelines for Clinical Care. University of Michigan Health System. Available at:
www.med.umich.edu/depression/depressguidelines04.pdf. Accessed June 28, 2007.
•Major Depressive Disorder: Practice Guidelines. American Psychiatric Association. Available at:
www.psych.org/psych_pract/treatg/pg/prac_guide.cfm. Accessed June 28, 2007.
•The MacArthur Foundation Initiative on Depression and Primary Care Depression Tool Kit. Available at:
www.depression-primarycare.org/clinicians/toolkits. Accessed June 28, 2007.
FOR MORE INFORMATION:
•Khouzam HR, Tan DT, Gill TS. Handbook of Emergency Psychiatry. Philadelphia: Mosby; 2007.
REFERENCES:
1. Wells KB, Stewart A, Hays RD, et al. The func-tioning and well-being of depressed patients: results from the Medical Outcomes Study. JAMA. 1989;262:914-919.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). 4th ed. Washington, DC: American Psych-iatric Association; 2000.
3. Schulberg HC, Katon W, Simon GE, Rush AJ.
Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research practice guidelines. Arch Gen Psychiatry. 1998;55:1121-1127.
4. Thase ME, Fava M, Halbreich U, et al. A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. Arch Gen Psychiatry. 1996;53:777-784.
5. Williams JW, Mulrow CD, Kroenke K, et al. Case-finding for depression in primary care: a randomized trial. Am J Med. 1999;106:36-43.
6. Whooley MA, Simon GE. Managing depression in medical outpatients. N Engl J Med. 2000;343: 1942-1950.
7. Simon GE, Katon W, Rutter C, et al. Impact of improved depression treatment in primary care on daily functioning and disability. Psychol Med. 1998; 28:693-701.
8. Depression Guideline Panel. Depression in Primary Care. Clinical practice guideline, no. 5. Rockville, Md: US Department of Health Services, Agency for Health Care Research and Quality; April. AHRQ publication 93-0551.
9. Gorman JM, Kent JM. SSRIs and SNRIs: broad spectrum of efficacy beyond major depression. J Clin Psychiatry. 1999;60(suppl 4):33-39.
10. Khouzam HR, Field S. Somatization disorder: clinical presentation and treatment in primary care. Hospital Physician. 1999;35(4):20-25.
11. Kendler KS, Gardner CO Jr. Boundaries of major depression: an evaluation of DSM-IV criteria. Am J Psychiatry. 1998;155:172-177.
12. Judd LL, Akiskal HS. Delineating the longitudinal structure of depressive illness: beyond clinical subtypes and duration thresholds. Pharmacopsychiatry. 2000;33:3-7.
13. Miller MC, Paulsen RH. Suicide assessment in the primary care setting. In: Jacobs DG, ed. The Harvard Medical School Guide to Suicide Assessment and Intervention. San Francisco: Jossey-Bass; 1999: 520-539.
14. Brody DS, Thompson TL II, Larson DB, et al. Strategies for counseling depressed patients by primary care physicians. J Gen Intern Med. 1994;9: 569-575.
15. Khouzam HR. Chronic fatigue syndrome: update on diagnosis and treatment. Consultant. 2000;40: 1441-1450.
16. Khouzam HR, Donnelly NJ. Posttraumatic stress disorder. Safe, effective management in the primary care setting. Postgrad Med. 2001;110:60-78.
17. Zajecka JM, Beeler M. Improving long-term adherence to treatment in major depression. In: Alpert JE, Fava M, eds. Handbook of Chronic Depression. New York: Marcel Dekker, Inc; 2004:403-410.
18. Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001; 178:234-241.
19. Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308-315.
20. Simon GE, Heiligenstein JH, Grothaus L, et al. Should anxiety and insomnia influence antidepresant selection: a randomized comparison of fluoxetine and imipramine. J Clin Psychiatry. 1998;59:49-55.
21. Simon GE, Heiligenstein J, Revicki D, et al. Long-term outcomes of initial antidepressant drug choice in a "real world" randomized trial. Arch Fam Med. 1999;8:319-325.
22. Khouzam HR. Chronic pain and its management in primary care. South Med J. 2000;93:946-952.
23. Tummala R, Zajecka JM. Tricyclics: still solid performers for the savvy psychiatrist. Curr Psychiatry. 2002;1:1-7.
24. Thase ME. Long-term nature of depression. J Clin Psychiatry. 1999;60(suppl 14):3-9.
25. Zajecka JM. Clinical issues in long-term treatment with antidepressants. J Clin Psychiatry. 2000; 61(suppl 2):20-25.
26. Antonuccio DO, Danton WG, DeNelsky GY. Psychotherapy versus medication for depression: challenging the conventional wisdom with data. Professional Psychology: Research and Practice. 1995;26:574-585.
27. Murray MT. Natural Alternatives to Prozac. New York: Quill; 1996:174-175.
28. S-Adenosyl-l-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease. Summary, Evidence Report/Technology Assessment: Number 64. Rockville, Md: Agency for Healthcare Research and Quality; 2002. AHRQ publication 02-E033.
29. Thase ME. What role do atypical antipsychotic drugs have in treatment-resistant depression? J Clin Psychiatry. 2002;63:95-103.
30. Spiker DG, Perel JM, Hanin I, et al. The pharmacological treatment of delusional depression: part II. J Clin Psychopharmacol. 1986;6:339-342.
31. Task Force Report of the American Psychiatric Association. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training and Privileging. Washington, DC: American Psychiatric Association; 1990:61-62.
32. Berman RM, Narasimhan M, Sanacora G, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biol Psychiatry. 2000;47:332-337.
33. Silverstone PH. The mind, brain, body connection: treating people with depression in the 21st century. In: Program and abstracts of the International Congress of Biological Psychiatry; February 9-13, 2004; Sydney, Australia. Symposium 24.
34. FDA Public Health Advisory. Worsening depression and suicidality in patients being treated with antidepressant medications. March 22, 2004.
35.Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007;297:1683-1696.
36.Bonari L, Bennett H, Einarson A, Koren G. Risks of untreated depression during pregnancy. Can Fam Physician. 2004;50:37-39.
37.Chung TK, Lau TK, Yip AS, et al. Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes. Psychosom Med. 2001;63:830-834.
38. Austin MP, Mitchell PB. Use of psychotropic medications in breast-feeding women: acute and prophylactic treatment. Aust N Z J Psychiatry. 1998; 2:778-784.
39. Gentile S. Use of contemporary antidepressants during breastfeeding: a proposal for a specific safety index. Drug Saf. 2007;30:107-121.
