Multidisciplinary Approaches to Anxiety and Depression

1. Multidisciplinary Approaches to Anxiety and Depression Sara L. Warber, MD Glenn Burdick, PhD Brodie Burris, MSTCM Caroline Richardson, MD

2. St. John’s Wort & Depression • Meta-analysis: 23 studies, 1757 pts • Mild-mod depression • Superior to placebo, rrr =2.67 (1.78-4.01) • As effective as TCA’s , rrr=1.10 (0.93-1.31) • Fewer side effects than TCA’s • Dose: 0.4-2.7 mg Hypericin (standardized extract) Linde K, et al. BMJ 1996;313:253-8

3. St. John’s Wort and Sertraline Ineffective! • Multi-center, randomized controlled trial • St. John’s Wort vs. sertraline (Zoloft) vs. placebo • 8 week treatment period, 360 subjects • No difference in Hamilton Depression Scale • Significant difference in side effects • Placebo < SJW < Zoloft JAMA 2000; 287:1807-14

4. St. John’s Wort - Toxicology • Side effects • Theoretical risk - sunburn • Herb-drug interactions • Studies - digoxin, protease inhibitors, TCAs • Case reports - cyclosporine, warfarin, oral contraceptives, theophylline, SSRIs • Theoretical - iron Facts & Comparisons Review of Natural Products, Dec 2000.

5. German Commission E mild anxiety to induce sleep Fat-soluble lactones kavalactone most effective Kavalactone’s actions sedative anticonvulsant analgesic Powdered root 60-210 mg kavalactones daily (max 300mg/d) Kava (Piper methystictum)

6. Kava - Toxicology • Side effects (2.3%) • headache, dry scaly dermopathy, GI distress • Allergic rashes • 3 cases of dystonic reactions • 25 cases of liver toxicity • Drug interactions • Case report - sedative/hypnotics • Theoretical - other CNS active drugs

7. SAMe (S-adenosyl-L-methionine) • For depression, osteoarthritis, fibromyalgia • Rationale: methyl donor on paths of monoamines, neurotransmitters, & phospholipids • Depression: 200 - 800 mg 2x/day • Meta-analysis: superior to placebo, equal to TCAs • Side effects: flatulence, nausea, vomiting, diarrhea, anxiety, hypomania • If used w/ other anti-depressant  serotonin syndrome

8. Folate & Vitamin B12 • Levels low in 1/3 of depressed persons • Rationale: methyl donors,  SAMe • 800 micrograms of each (much higher doses used in studies) • High dose Folate: alters sleep pattern, vivid dreaming, irritability, seizure, GI disturbance, bitter taste in mouth

9. Vitamin B6 • Low in depressed patients (esp if taking estrogens) • Rationale: essential in serotonin synthesis • Vitamin B Complex 100 – provides 100 mg of major B vitamins • 200 mg daily  neurotoxicity

10. 5-HTP (Hydroxytryptophan) • Rationale: intermediate on pathway of tryptophan to serotonin, 70% conversion • Also  endorphins & catecholamines • 100-200mg 3x/day, enteric coated • As effective as SSRIs & TCAs • Avoid use w/ other antidepressants serotonin syndrome

11. Treating Depression with Physical Activity Caroline R. Richardson, MD Department of Family Medicine VA Health Services Research and Development Center

12. Blumenthal et alexercise vs. medication 156 men and women Over 50 years old Major depressive disorder by clinical interview, BDI, HAM-D Randomized to – aerobic exercise (n=53), - Zoloft ( n = 48) or - aerobic exercise + Zoloft (n=55) For 16 weeks Blumenthal et al 1999 Archives of Internal Medicine

13. The Exercise Intervention • 3 supervised exercise sessions / week • 10 minute warm up • 30 minutes walking or jogging at 70 to 85% of heart rate reserve. • 5 minute cool down • 16 weeks

14. Blumenthal’s Results Blumenthal et al Archives of Internal Medicine 1999:159:2349-2356.

15. Blumenthal’s Conclusion Exercise is as good as Zoloft in the treatment of Depression.

16. Correct Conclusion • Among highly motivated but depressed individuals, those who can successfully participate in a structured exercise program will probably significantly decrease their depressive symptoms.

17. Meta-Analysis • 14 Randomized Controlled Trials • All but two studies showed an independent, statistically and clinically significant improvement in depressive symptoms. • Effect Size -1.1 (95% CI -1.5 to -0.7) • Comparing Exercise to No treatment Control Lawlor, DA BMJ March 2001

18. 100’s of Observational Studies • People who are not depressed now but are physically active now are less likely to be depressed in the future. • Physical Activity reduces depression relapse • College students who were physically active are less likely to become depressed later

19. One more point. • We know that it is hard to start an exercise program and harder to stick with it. • How many of our depressed patients successfully initiate and maintain a medication program? 20% to 60% stop taking med in 1st week.

20. How Can You Help Depressed Patients Become More Active • Recommend exercise and say that there are some clinical trials showing exercise reduces depression symptoms. • Write out an exercise prescription along with the anti-depressant script • Discuss types of exercise, Ways of fitting in exercise, How to get started

21. PEDOMETERS • Count Daily Steps and record on a calendar • Bring in Calendar to review after one week • Obese patients may not get accurate step counts • Caution with 10,000 steps a day target! • Wear the pedometer all day every day • Digi-walker SW200 ($20.00)

22. Watch out for Biases • Who do we think will not or should not exercise • Poor patients • Sick patients • Minority Groups • Older patients • Depressed Patients

23. More Reasons for Depressed Patients to Exercise • Medications for Depression cause weight gain, diabetes • Number 1 cause of death in depressed patients is still heart disease. • Diabetes is about 2 x as prevalent in depressed patients as it is among non-depressed patients.