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Sertraline treatment and weight loss
CURRENT THERAPEUTIC RESEARCH VOL. 55, NO. 10, OCTOBER1994
SERTRALINE TREATMENT AND WEIGHT LOSS W A Y N E MEYEROWITZ A N D J A M E S D. C. J A R A M I L L O
Medical Institute for Mental Health, Albuquerque, New Mexico
ABSTRACT
Weight gain is a common complaint of patients receiving antidepressant drug treatment. The antidepressant sertraline, a selective serotonin uptake inhibitor, has been reported to promote weight loss. In this study, measurement of urinary concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) was used to help classify the response of patients who were depressed and overweight to treatment with sertraline. The authors found a significant difference between the average weight loss of 1.06 lb/week in patients with a low urinary MHPG and the average weight loss of 0.42 lb/week in those with a high urinary MHPG. During this study, the maximum weight loss by a patient was 69 pounds over 36 weeks. INTRODUCTION
Clinical depression may be considered a prolonged state of lowered mood that is not easily changed by environmental events. 1 A major symptom of depression is a change in appetite that leads to either weight gain or weight loss. 2'3 Weight gain is also a common complaint of patients receiving antidepressant drug treatment. 4-6 These patients frequently report that sweet-tasting and carbohydrate-containing foods become irresistible. 5'7'8 The resulting unwanted weight gain can lead to extreme frustration and a lack of patient compliance with the treatment process. 9 An antidepressant that could improve mood and prevent weight gain or promote weight loss would be of value in the management of the overweight depressed patient. 1° Sertraline has been reported to promote weight loss. 11-19 This antidepressant medication is a selective serotonin uptake inhibitor. It also acts weakly on the uptake of dopamine and norepinephrine.11'17'18 In recent years, considerable research has centered on developing laboratory tests for the diagnosis of depression and the assessment and verification of the response to treatment. 3-Methoxy-4-hydroxyphenylglycol (MHPG) has served as a useful clinical guide for selecting an antidepressant for treatment. Several investigators have reported that urinary exAddress correspondence to: Dr. Wayne Meyerowitz, Director of Research, Medical Institute for Mental Health, 500 Chama NE, Albuquerque, NM 87108. Received for publication on August 10, 1994. Printed in the U.S.A. Reproduction in whole or part is not permitted. 1176
0011-393X]94/$3.50
W. MEYEROWITZAND J. D~C. JARAMILLO
cretion of MHPG, the primary metabolite of norepinephrine, 19-26 is reduced in p a t i e n t s who t e n d to respond t o a n t i d e p r e s s a n t s such as protriptyline that stimulate the norepinephrine system in the brain. In contrast, patients who excrete high amounts of MHPG appear to respond better to antidepressants such as sertraline that affect the serotonin s y s t e m . 27-31
The current study was designed to examine the effectiveness of sertraline in treating overweight depressed patients. In particular, our plan was to use measurements of urinary M H P G excretion as a guide to classify which patients responded more effectively in relation to weight loss.
P A T I E N T S AND M E T H O D S
Twenty-three outpatients who met the criteria for major depression as classified in the Diagnostic and Statistical Manual of Mental Disorders, Third E d i t i o n - - R e v i s e d 32 were entered into the study. An additional inclusion criterion was that patients had to be at least 20 pounds over the acceptable range for their usual weight as recommended by the First Fogerty Conference on Obesity. 33 The study patients included 19 women and 4 men between the ages of 19 and 60 years. All patients had unipolar depression and presented with either a single or a recurrent episode. At the onset of the study, patients were excluded if they took medication or had a medical condition that might interfere with their initial neurochemical test results. The protocol for the study was initiated by instructing each patient to collect a 24-hour urine sample for measurement of M H P G concentrations. The samples were refrigerated, and aliquots were frozen at - 20 °C within 3 days. Completeness of the urine collection was ascertained by careful interview and by measurements of the 24-hour volume and the creatine excretion. Biochemical determinations were performed by laboratory personnel blind to clinical diagnosis. For the purpose of this study, abnormalities of urinary M H P G excretion and resultant categories of low or high M H P G were defined as follows: women, <1100 or >1560 ~g/24 h, and men, <1250 or >2140 ~g/24 h. Sertraline dosages ranged from 5 0 - 2 0 0 mg/d for 8 to 61 weeks. The patients were told that sertraline is an approved medication for treating depression and that it might promote weight loss. They were given no special dietary or exercise instructions. The patients were also instructed to follow their regular therapy program throughout the course of the study. At each session, they were weighed, and their total situation was reviewed. All patients provided informed consent prior to participating in the study. 1177
SERTRALINETREATMENTANDWEIGHTLOSS
RESULTS
All participants in this study completed a 24-hour urine collection for measurement of MHPG and recorded their baseline weight to initiate the study protocol; however, three patients subsequently withdrew from the study. Data for the mean 24-hour urinary MHPG values stratified by high and low categories are shown in Figure 1. The mean value of patients in the low MHPG category was 682 ~g/24 h whereas the mean value of patients in the high MHPG category was 2130 ~g/24 h. The average dose of sertraline for the high MHPG category was 136 mg/d whereas the average dose for the low MHPG category was 110 r~g/d. A significant difference was seen between these two doses of sertraline (t = 5.92, P < 0.001). Results reflecting weight loss are illustrated in Figure 2. The average weight loss of 1.06 lb/week in patients with low urinary levels of MHPG was significantly greater than the average weight loss of 0.42 lb/week in patients with high urinary levels ofMHPG (t = 2.76, P < 0.02). During the course of this study, the maximum weight loss by a patient was 69 pounds over 36 weeks. The average improvement in the presenting depression was moderate in both MHPG categories as determined by using both the Hamilton Depression Rating Scale and a general depression checklist used at the Medical Institute for Mental Health, where this study was conducted.
-~
2,200
~
LowMHPG (N=11)
2,000
--~
HighMHPG (N = 9)
1,800 1,600 1,400 2" 1,200 1,000 8O0 600 400 2OO
Figure 1. Mean (-+SD) 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG).
1178
W. M E Y E R O W I T Z A N D J . D. C. J A R A M I L L O
1.75
Low MHPG (n = 11)
1.50 High MHPG (n = 9)
1.25 1.00
o, f,,
0.75
/¢7"/O/I
0.50 0.25
/ /
Figure 2. Average weight loss. MHPG = 3-methoxy-4-hydroxyphenylglycol.
DISCUSSION AND CONCLUSION
In this study, we found that depressed patients receiving the antidepressant sertraline could lose weight during the therapeutic process. The results also showed that there was a significant difference in the average weight loss of 1.06 lb/week in patients with low urinary levels of MHPG compared with the average weight loss of 0.42 lb/week in patients with high urinary levels of MHPG. Furthermore, a significantly smaller dose of sertraline was needed for patients in the low MHPG category. The observed weight loss provided significant evidence of an effect of the medication on eating behavior. Equally impressive were comments from the patients that their desire for sweet-tasting and carbohydrate-containing foods was greatly reduced. In conclusion, it was interesting to find that sertraline, a predominantly selective serotonin uptake inhibitor, had a greater effect on weight loss in depressed overweight patients with a low urinary level of MHPG. One possible explanation for this is provided by reports that sertraline acts weakly on the uptake of norepinephrine. There also appears to be some interaction between the norepinephrine and serotonin systems in the brain. Reports of data exist suggesting the possibility of a mutual regulatory effect of the serotonin and norepinephrine neuronal systems. 34 When using the MHPC test as a guide, this new information on the weight-loss promoting capabilities of sertraline has been seen as an important addition to the initial clinical judgment and other medical and psychological information available to the attending psychiatrist. Additional studies are necessary to build on these findings and to optimize the therapeutic process for treating depression with resultant weight loss.
1179
SERTRALINE T R E A T M E N T A N D W E I G H T LOSS
References: 1. Siever LJ, Davis KL, Gorman LK. Pathogenesis of mood disorders. In: Davis KL, Klar H, Coyle JT, eds. Foundations of Psychiatry. Philadelphia, Pa: WB Saunders; 1991:254-255. 2. Kaplan HI, Sadock BJ. Pocket Handbook of Clinical Psychiatry. Baltimore, Md: Williams & Williams; 1990. 3. Orzack HM, Cole JO, Fiedman L, et al. Weight changes in antidepressants: A comparison of amitriptyline and trazodone. Neuropsychobiology. 1986;15:28-30. 4. Fernstrom MH, Kupfer DJ. Antidepressant-induced weight gain: A comparison study of four medications. Psychiatry Res. 1988;26:265-271. 5. Garland EJ, Remick RA, Zis AP. Weight gain with antidepressants and lithium. J Clin Psychopharmacol. 1988;8:323-330. 6. Frankle RT, Yang M-U. Obesity and Weight Control--the Health Professional's Guide to Understanding and Treatment. Gaithersburg, Md: Aspen; 1987. 7. Kalucy RS. Drug-induced weight gain. Drugs. 1980;19:268-278. 8. Paykel ES, Mueller PS, De La Vergne PM. Amitriptyline, weight gain and carbohydrate craving: A side effect. Br J Psychiatry. 1973;123:501-507. 9. Meyerowitz W, Jaramillo JDC. Antidepressant treatment and weight loss. Curr Ther Res. 1992;52:169-174. 10. Abell CA, Farquhar DL, Galloway SM, et al. Placebo-controlled double-blind trial of fluvoxamine maleate in the obese. J Psychosom Res. 1986;30:143-146. 11. Guthrie SK. Sertraline: A new specific serotonin reuptake blocker. Ann Pharmacother. 1991;25:952-961. 12. Rickels K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry. 1990;51:9-12. 13. Koe BK. Preclinical pharmacology of sertraline: A potent and specific inhibitor of serotonin reuptake. J Clin Psychiatry. 1990;51:13-17. 14. Kasper S, Fuger J, Moller HJ. Comparative efficacy of antidepressants. Drugs. 1992;43: 11-23. 15. Auster R. Sertraline: A new antidepressant. A m Fam Physician. 1993;48:311-314. 16. Ayd F. Sertraline: The latest FDA-approved serotonin uptake inhibitor antidepressant. International Drug Therapy Newsletter. 1992;27:9-12. 17. Garattini S, Mennini T, Samanin R. Reduction of food intake by manipulation of central serotonin. Br J Psychiatry. 1989;155:41-51. 18. Reimherr FW, Chouinard G, Cohn CK, et al. Antidepressant efficacy of sertraline: A double-blind, placebo- and amitriptyline-controlled,multicenter comparison study in out, patients with major depression. J Clin Psychiatry. 1990;51:18-27. 19. Pottash ALC, Gold MS, Extein I. The use of the clinical laboratory. In: Sederer LI, ed. Inpatient Psychiatry Diagnosis and Treatment. Baltimore, Md: Waverly Press Inc; 1983: 205-220. 20. Ward NG, Bloom VL, Dworkin S, et al. Psychobiological markers in coexisting pain and depression: Toward a unified theory. J Clin Psychiatry. 1982;43:32-40. 1180
w. MEYEROWITZANDJ. D.C. JARAMILLO
21. Maas JW. Clinical and biochemical heterogeneity of depressive disorders. Ann Intern Med. 1978;88:556-563. 22. Orsulak PJ, Schatzberg AF, Grab FL, Schildkraut JJ. Urinary MHPG as predictors of response to the antidepressant maprotiline. Am Assoc Clin Chem. 1982;28:1-5. 23. Lader M. Antidepressant drugs. In: Introduction to Psychopharmacology--a Scope Publication. Kalamazoo, Mi: Upjohn; 1983:68-89. 24. Roy A, Pickar D, Paul S. Biologic tests in depression. Psychosomatics. 1984;25:443-451. 25. Davis RE, Wengert JW. Biochemical theories of depression. Physician Assistant. 1987; 11:25-40. 26. Garvey MJ, Hollon S, Evans M, et al. The association of MHPG to dexamethasone suppression test status. Psychiatry Res. 1988;24:223-230. 27. Brown WA, Qualis CB. Pituitary-adrenal disinhibition in depression: Marker of a subtype with characteristic clinical features and response to treatment. Psychiatry Res. 1981;4:115-128. 28. Maas JW, Koslow SH, Katz MM, et al. Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. A m J Psychiatry. 1984;141:1159-1171. 29. Ortrow DG, Okenek A, Gibbons R, et al. Biologic markers and antidepressant response. J Clin Psychiatry. 1983;44:10-13. 30. Hirschfeld RMA, Lobel B. Depression--what we know. U.S. Department of Health and Human Services; 1984:27-30. 31. Van Pragg HM. The significance of biologic factors in the diagnosis of depressions. I. Biological variables. Compr Psychiatry. 1982;23:124-135. 32. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. revised. Washington, DC: American Psychiatric Association; 1987. 33. Alpers DH, Clouse RE, Stenson WF. Manual of Nutritional Therapeutics. Baltimore, Md: Little, Brown and Company; 1988. 34. Maas JW, Katz MM, Frazer A, et al. Current evidence regarding biological hypotheses of depression and accompanying pathophysiological processes: A critique and synthesis of results using clinical and basic research results. Integrative Psychiatry. 1991;7:155-169.
1181
SERTRALINE TREATMENT AND WEIGHT LOSS W A Y N E MEYEROWITZ A N D J A M E S D. C. J A R A M I L L O
Medical Institute for Mental Health, Albuquerque, New Mexico
ABSTRACT
Weight gain is a common complaint of patients receiving antidepressant drug treatment. The antidepressant sertraline, a selective serotonin uptake inhibitor, has been reported to promote weight loss. In this study, measurement of urinary concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) was used to help classify the response of patients who were depressed and overweight to treatment with sertraline. The authors found a significant difference between the average weight loss of 1.06 lb/week in patients with a low urinary MHPG and the average weight loss of 0.42 lb/week in those with a high urinary MHPG. During this study, the maximum weight loss by a patient was 69 pounds over 36 weeks. INTRODUCTION
Clinical depression may be considered a prolonged state of lowered mood that is not easily changed by environmental events. 1 A major symptom of depression is a change in appetite that leads to either weight gain or weight loss. 2'3 Weight gain is also a common complaint of patients receiving antidepressant drug treatment. 4-6 These patients frequently report that sweet-tasting and carbohydrate-containing foods become irresistible. 5'7'8 The resulting unwanted weight gain can lead to extreme frustration and a lack of patient compliance with the treatment process. 9 An antidepressant that could improve mood and prevent weight gain or promote weight loss would be of value in the management of the overweight depressed patient. 1° Sertraline has been reported to promote weight loss. 11-19 This antidepressant medication is a selective serotonin uptake inhibitor. It also acts weakly on the uptake of dopamine and norepinephrine.11'17'18 In recent years, considerable research has centered on developing laboratory tests for the diagnosis of depression and the assessment and verification of the response to treatment. 3-Methoxy-4-hydroxyphenylglycol (MHPG) has served as a useful clinical guide for selecting an antidepressant for treatment. Several investigators have reported that urinary exAddress correspondence to: Dr. Wayne Meyerowitz, Director of Research, Medical Institute for Mental Health, 500 Chama NE, Albuquerque, NM 87108. Received for publication on August 10, 1994. Printed in the U.S.A. Reproduction in whole or part is not permitted. 1176
0011-393X]94/$3.50
W. MEYEROWITZAND J. D~C. JARAMILLO
cretion of MHPG, the primary metabolite of norepinephrine, 19-26 is reduced in p a t i e n t s who t e n d to respond t o a n t i d e p r e s s a n t s such as protriptyline that stimulate the norepinephrine system in the brain. In contrast, patients who excrete high amounts of MHPG appear to respond better to antidepressants such as sertraline that affect the serotonin s y s t e m . 27-31
The current study was designed to examine the effectiveness of sertraline in treating overweight depressed patients. In particular, our plan was to use measurements of urinary M H P G excretion as a guide to classify which patients responded more effectively in relation to weight loss.
P A T I E N T S AND M E T H O D S
Twenty-three outpatients who met the criteria for major depression as classified in the Diagnostic and Statistical Manual of Mental Disorders, Third E d i t i o n - - R e v i s e d 32 were entered into the study. An additional inclusion criterion was that patients had to be at least 20 pounds over the acceptable range for their usual weight as recommended by the First Fogerty Conference on Obesity. 33 The study patients included 19 women and 4 men between the ages of 19 and 60 years. All patients had unipolar depression and presented with either a single or a recurrent episode. At the onset of the study, patients were excluded if they took medication or had a medical condition that might interfere with their initial neurochemical test results. The protocol for the study was initiated by instructing each patient to collect a 24-hour urine sample for measurement of M H P G concentrations. The samples were refrigerated, and aliquots were frozen at - 20 °C within 3 days. Completeness of the urine collection was ascertained by careful interview and by measurements of the 24-hour volume and the creatine excretion. Biochemical determinations were performed by laboratory personnel blind to clinical diagnosis. For the purpose of this study, abnormalities of urinary M H P G excretion and resultant categories of low or high M H P G were defined as follows: women, <1100 or >1560 ~g/24 h, and men, <1250 or >2140 ~g/24 h. Sertraline dosages ranged from 5 0 - 2 0 0 mg/d for 8 to 61 weeks. The patients were told that sertraline is an approved medication for treating depression and that it might promote weight loss. They were given no special dietary or exercise instructions. The patients were also instructed to follow their regular therapy program throughout the course of the study. At each session, they were weighed, and their total situation was reviewed. All patients provided informed consent prior to participating in the study. 1177
SERTRALINETREATMENTANDWEIGHTLOSS
RESULTS
All participants in this study completed a 24-hour urine collection for measurement of MHPG and recorded their baseline weight to initiate the study protocol; however, three patients subsequently withdrew from the study. Data for the mean 24-hour urinary MHPG values stratified by high and low categories are shown in Figure 1. The mean value of patients in the low MHPG category was 682 ~g/24 h whereas the mean value of patients in the high MHPG category was 2130 ~g/24 h. The average dose of sertraline for the high MHPG category was 136 mg/d whereas the average dose for the low MHPG category was 110 r~g/d. A significant difference was seen between these two doses of sertraline (t = 5.92, P < 0.001). Results reflecting weight loss are illustrated in Figure 2. The average weight loss of 1.06 lb/week in patients with low urinary levels of MHPG was significantly greater than the average weight loss of 0.42 lb/week in patients with high urinary levels ofMHPG (t = 2.76, P < 0.02). During the course of this study, the maximum weight loss by a patient was 69 pounds over 36 weeks. The average improvement in the presenting depression was moderate in both MHPG categories as determined by using both the Hamilton Depression Rating Scale and a general depression checklist used at the Medical Institute for Mental Health, where this study was conducted.
-~
2,200
~
LowMHPG (N=11)
2,000
--~
HighMHPG (N = 9)
1,800 1,600 1,400 2" 1,200 1,000 8O0 600 400 2OO
Figure 1. Mean (-+SD) 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG).
1178
W. M E Y E R O W I T Z A N D J . D. C. J A R A M I L L O
1.75
Low MHPG (n = 11)
1.50 High MHPG (n = 9)
1.25 1.00
o, f,,
0.75
/¢7"/O/I
0.50 0.25
/ /
Figure 2. Average weight loss. MHPG = 3-methoxy-4-hydroxyphenylglycol.
DISCUSSION AND CONCLUSION
In this study, we found that depressed patients receiving the antidepressant sertraline could lose weight during the therapeutic process. The results also showed that there was a significant difference in the average weight loss of 1.06 lb/week in patients with low urinary levels of MHPG compared with the average weight loss of 0.42 lb/week in patients with high urinary levels of MHPG. Furthermore, a significantly smaller dose of sertraline was needed for patients in the low MHPG category. The observed weight loss provided significant evidence of an effect of the medication on eating behavior. Equally impressive were comments from the patients that their desire for sweet-tasting and carbohydrate-containing foods was greatly reduced. In conclusion, it was interesting to find that sertraline, a predominantly selective serotonin uptake inhibitor, had a greater effect on weight loss in depressed overweight patients with a low urinary level of MHPG. One possible explanation for this is provided by reports that sertraline acts weakly on the uptake of norepinephrine. There also appears to be some interaction between the norepinephrine and serotonin systems in the brain. Reports of data exist suggesting the possibility of a mutual regulatory effect of the serotonin and norepinephrine neuronal systems. 34 When using the MHPC test as a guide, this new information on the weight-loss promoting capabilities of sertraline has been seen as an important addition to the initial clinical judgment and other medical and psychological information available to the attending psychiatrist. Additional studies are necessary to build on these findings and to optimize the therapeutic process for treating depression with resultant weight loss.
1179
SERTRALINE T R E A T M E N T A N D W E I G H T LOSS
References: 1. Siever LJ, Davis KL, Gorman LK. Pathogenesis of mood disorders. In: Davis KL, Klar H, Coyle JT, eds. Foundations of Psychiatry. Philadelphia, Pa: WB Saunders; 1991:254-255. 2. Kaplan HI, Sadock BJ. Pocket Handbook of Clinical Psychiatry. Baltimore, Md: Williams & Williams; 1990. 3. Orzack HM, Cole JO, Fiedman L, et al. Weight changes in antidepressants: A comparison of amitriptyline and trazodone. Neuropsychobiology. 1986;15:28-30. 4. Fernstrom MH, Kupfer DJ. Antidepressant-induced weight gain: A comparison study of four medications. Psychiatry Res. 1988;26:265-271. 5. Garland EJ, Remick RA, Zis AP. Weight gain with antidepressants and lithium. J Clin Psychopharmacol. 1988;8:323-330. 6. Frankle RT, Yang M-U. Obesity and Weight Control--the Health Professional's Guide to Understanding and Treatment. Gaithersburg, Md: Aspen; 1987. 7. Kalucy RS. Drug-induced weight gain. Drugs. 1980;19:268-278. 8. Paykel ES, Mueller PS, De La Vergne PM. Amitriptyline, weight gain and carbohydrate craving: A side effect. Br J Psychiatry. 1973;123:501-507. 9. Meyerowitz W, Jaramillo JDC. Antidepressant treatment and weight loss. Curr Ther Res. 1992;52:169-174. 10. Abell CA, Farquhar DL, Galloway SM, et al. Placebo-controlled double-blind trial of fluvoxamine maleate in the obese. J Psychosom Res. 1986;30:143-146. 11. Guthrie SK. Sertraline: A new specific serotonin reuptake blocker. Ann Pharmacother. 1991;25:952-961. 12. Rickels K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry. 1990;51:9-12. 13. Koe BK. Preclinical pharmacology of sertraline: A potent and specific inhibitor of serotonin reuptake. J Clin Psychiatry. 1990;51:13-17. 14. Kasper S, Fuger J, Moller HJ. Comparative efficacy of antidepressants. Drugs. 1992;43: 11-23. 15. Auster R. Sertraline: A new antidepressant. A m Fam Physician. 1993;48:311-314. 16. Ayd F. Sertraline: The latest FDA-approved serotonin uptake inhibitor antidepressant. International Drug Therapy Newsletter. 1992;27:9-12. 17. Garattini S, Mennini T, Samanin R. Reduction of food intake by manipulation of central serotonin. Br J Psychiatry. 1989;155:41-51. 18. Reimherr FW, Chouinard G, Cohn CK, et al. Antidepressant efficacy of sertraline: A double-blind, placebo- and amitriptyline-controlled,multicenter comparison study in out, patients with major depression. J Clin Psychiatry. 1990;51:18-27. 19. Pottash ALC, Gold MS, Extein I. The use of the clinical laboratory. In: Sederer LI, ed. Inpatient Psychiatry Diagnosis and Treatment. Baltimore, Md: Waverly Press Inc; 1983: 205-220. 20. Ward NG, Bloom VL, Dworkin S, et al. Psychobiological markers in coexisting pain and depression: Toward a unified theory. J Clin Psychiatry. 1982;43:32-40. 1180
w. MEYEROWITZANDJ. D.C. JARAMILLO
21. Maas JW. Clinical and biochemical heterogeneity of depressive disorders. Ann Intern Med. 1978;88:556-563. 22. Orsulak PJ, Schatzberg AF, Grab FL, Schildkraut JJ. Urinary MHPG as predictors of response to the antidepressant maprotiline. Am Assoc Clin Chem. 1982;28:1-5. 23. Lader M. Antidepressant drugs. In: Introduction to Psychopharmacology--a Scope Publication. Kalamazoo, Mi: Upjohn; 1983:68-89. 24. Roy A, Pickar D, Paul S. Biologic tests in depression. Psychosomatics. 1984;25:443-451. 25. Davis RE, Wengert JW. Biochemical theories of depression. Physician Assistant. 1987; 11:25-40. 26. Garvey MJ, Hollon S, Evans M, et al. The association of MHPG to dexamethasone suppression test status. Psychiatry Res. 1988;24:223-230. 27. Brown WA, Qualis CB. Pituitary-adrenal disinhibition in depression: Marker of a subtype with characteristic clinical features and response to treatment. Psychiatry Res. 1981;4:115-128. 28. Maas JW, Koslow SH, Katz MM, et al. Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. A m J Psychiatry. 1984;141:1159-1171. 29. Ortrow DG, Okenek A, Gibbons R, et al. Biologic markers and antidepressant response. J Clin Psychiatry. 1983;44:10-13. 30. Hirschfeld RMA, Lobel B. Depression--what we know. U.S. Department of Health and Human Services; 1984:27-30. 31. Van Pragg HM. The significance of biologic factors in the diagnosis of depressions. I. Biological variables. Compr Psychiatry. 1982;23:124-135. 32. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. revised. Washington, DC: American Psychiatric Association; 1987. 33. Alpers DH, Clouse RE, Stenson WF. Manual of Nutritional Therapeutics. Baltimore, Md: Little, Brown and Company; 1988. 34. Maas JW, Katz MM, Frazer A, et al. Current evidence regarding biological hypotheses of depression and accompanying pathophysiological processes: A critique and synthesis of results using clinical and basic research results. Integrative Psychiatry. 1991;7:155-169.
1181