ORIGINAL ARTICLE Treatment of Atypical Depression With Cognitive Therapy or Phenelzine A Double-blind, Placebo-Controlled Trial Robin B. Jarrett, PhD; Martin Schaffer, MD; Donald McIntire, PhD; Amy Witt-Browder, MA; Dolores Kraft, PhD; Richard C. Risser, MS Background: Patients with atypical depression are more Results: With the use of an intention-to-treat strategy, likely to respond to monoamine oxidase inhibitors than the response rates (21-item Hamilton Rating Scale for De- to tricyclic antidepressants. They are frequently offered pression score, #9) were significantly greater after cog- psychotherapy in the absence of controlled tests. There nitive therapy (58%) and phenelzine (58%) than after pill are no prospective, randomized, controlled trials, to our placebo (28%). Phenelzine and cognitive therapy also re- knowledge, of psychotherapy for atypical depression or duced symptoms significantly more than placebo accord- of cognitive therapy compared with a monoamine oxi- ing to contrasts after a repeated-measures analysis of co- dase inhibitor. Since there is only 1 placebo-controlled variance and random regression with the use of the blind trial of cognitive therapy, this trial fills a gap in the lit- evaluator’s final Hamilton Rating Scale for Depression score. erature on psychotherapy for depression. The scores between cognitive therapy and phenelzine did not differ significantly. Supplemental analyses of other Methods: Outpatients with DSM-III-R major depres- symptom severity measures confirm the finding. sive disorder and atypical features (N = 108) were treated in a 10-week, double-blind, randomized, controlled trial Conclusions: Cognitive therapy may offer an effective comparing acute-phase cognitive therapy or clinical man- alternative to standard acute-phase treatment with a agement plus either phenelzine sulfate or placebo. Atypi- monoamine oxidase inhibitor for outpatients with ma- cal features were defined as reactive mood plus at least 2 jor depressive disorder and atypical features. additional symptoms: hypersomnia, hyperphagia, leaden paralysis, or lifetime sensitivity to rejection. Arch Gen Psychiatry. 1999;56:431-437 ATIENTS WITH majordepressive than waiting-list controls,15 has not dif- disorder (MDD) and atypical fered significantly from antidepressant features have shown a prefer- medication used alone,12,16-19 and may not ential response to phenelzine differ when combined with pharmaco- sulfate compared with imipra- therapy.12,19,20 mine hydrochloride in placebo-controlled We defined atypical features as a sub- P1-7 trials, prompting the recommendation of type of MDD during which patients have monoamine oxidase inhibitors (MAOIs) as reactive mood and at least 2 of the follow- the standard of care.8 Unfortunately, MAOIs ing 4 symptoms: hyperphagia, hypersom- have dietary restrictions, contraindications, nia, leaden paralysis, or a lifetime history and well-known side effects.3,9 Although Re- of interpersonal sensitivity to rejection, re- imherr et al10 and Pande et al11 showed that sulting in functional impairment. This de- fluoxetine hydrochloride may offer an al- finition is comparable with that used in ternative, many patients cannot or will not DSM-IV21 and has heuristic value in select- take antidepressant medication. Since psy- ing patients who respond to phenelzine. chosocial treatments are sought by and pre- The purpose of this double-blind, pla- scribed for depressed patients with atypical cebo-controlled trial of outpatients with features, studies of efficacy and effectiveness MDD and atypical features was to com- are needed. pare acute-phase cognitive therapy with Cognitive therapy is effective for some the standard of care, phenelzine. Phenel- patients with MDD.12,13 Mercier and col- zine was selected instead of a selective se- leagues14 showed that cognitive therapy re- rotonin reuptake inhibitor because there From the Department of duced symptoms of depressed outpa- is more support for its efficacy in this pa- 1-7 Psychiatry, The University of tients with atypical features. In depressed tient population. We hypothesized that Texas Southwestern Medical outpatients who were not subtyped, acute- cognitive therapy and phenelzine would Center at Dallas. phase cognitive therapy is more effective each reduce depressive symptoms signifi- ARCH GEN PSYCHIATRY/ VOL 56, MAY 1999 431 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 PATIENTS AND METHODS Of the 366 patients studied, 287 (78.4%) were diagnosed as having MDD; of the patients with MDD, 242 (66.1% of those studied) were also diagnosed as having atypical de- PATIENTS pression. One hundred eighty-one (49.5%) were eligible. Thirty-nine (21.5%) refused consent (generally because of The protocol was approved by the institutional review scheduling problems or the desire to receive or avoid a study board. Subjects (recruited through media, printed treatment). The nonspecific treatment baseline (designed announcements, and self or practitioner referrals) under- to identify and exclude patients who respond to early, non- went triage by telephone. Outpatients (N = 366) with the specific effects) was initiated when patients signed consent complaint of depression participated in the Structured (n = 142). Subjects participated in 2 sessions (during 14 days) Clinical Interview for DSM-III-R (Outpatient Version),22 of nonspecific treatment by watching a videotape on mood which uses the DSM-III-R23 criteria for MDD and other disorders and reporting on symptoms from the HRSD-21. disorders. To assess MDD with atypical features, the At the end of nonspecific treatment, 13 patients had responded Atypical Depression Diagnostic Scale (Jonathan W. Stew- (ie, HRSD-21 ,14 or no MDD) and were referred. art, MD, written communication, October 20, 1988, and Final eligibility for randomization was evaluated by March 20, 1990) was administered for the initial episode. confirming that the inclusion criteria were met. One hun- If the diagnosis was absent at the nadir, symptoms were dred eight (76.0% of the consenting and eligible) patients reassessed at “any other time during the episode.” Criteria were randomized (Table 1) under the supervision of the (according to the Atypical Depression Diagnostic Scale) statistician (D.M.), who kept research personnel blind to for depression with atypical features included (1) main- assignment (phenelzine or placebo) during the study. tains reactive mood and (2) shows 2 or more of the fol- lowing: (a) increased appetite or weight gain; (b) over- TREATMENT PROCEDURES sleeping; (c) sensation of leaden paralysis or extreme heaviness of arms or legs, while depressed; and (d) life- Cognitive Therapy time sensitivity to interpersonal rejection.1,2 Diagnoses were confirmed by a faculty-level diagnos- Cognitive therapy was conducted as described by Beck et tician at a follow-up interview. Entry criteria were (1) DSM- al29 for 10 weeks, in 20 individual sessions held twice weekly. III-R MDD, (2) definite atypical depression, and (3) score Three experienced male therapists provided cognitive of 14 or more on the 21-item Hamilton Rating Scale for De- therapy. Two were doctoral-level clinical psychologists and pression (HRSD-21)24 at the initial or follow-up inter- 1 was a psychiatrist. An offsite consultant (see acknowl- view. All patients provided a medical history and a physi- edgments) used the Cognitive Therapy Scale30,31 to evalu- cian reviewed laboratory screening. ate competence and provide feedback to therapists and in- Patients were excluded if they (1) had a concurrent vestigators. medical disorder or treatment that might cause depressive Therapists participated in weekly group supervision. symptoms or required medication incompatible with Of 64 total Cognitive Therapy Scale ratings (ie, 2 planned MAOIs; (2) refused to be randomized or to maintain a ty- per patient), 9 (14%) received scores of less than 40. The ramine-free diet; (3) had other current primary comorbid grand mean Cognitive Therapy Scale score across all thera- psychiatric disorders (eg, organic mental disorders, psy- pists was 46.1 ± 4.1. The analyses of variance showed no chotic disorders, schizophrenia, schizoaffective disorders, statistically significant differences in the mean Cognitive alcoholism, or drug abuse or dependency in the last 6 Therapy Scale scores among therapists (F2 = 2.50; P = .09) months); (4) scored less than 14 on the HRSD-21 at diag- or across years (F4 = 1.40; P = .24). nostic evaluation and follow-up, or before randomization (see description of nonspecific treatment below); (5) could Phenelzine and Placebo not complete questionnaires; (6) represented an immi- nent suicide risk; or (7) had previously had an adequate A treatment manual32 modeled after the National Institute trial of MAOIs or cognitive therapy that failed. of Mental Health Treatment of Depression Collaborative 2 cantly more than placebo and that the active treatments (x 2 = 22.04; P#.001). Five patients (14%) dropped out would produce comparable reductions. of cognitive therapy, 9 (25%) from phenelzine, and 23 (64%) from placebo. Attrition in the placebo group was RESULTS significantly greater than in cognitive therapy 2 2 (x 1 = 18.94; P#.001) and phenelzine (x 1 = 11.03; SAMPLE DESCRIPTION P#.001). The attrition between active treatments did 2 not differ significantly (x 1 = 1.42; P = .23). Of patients One hundred forty-two outpatients with MDD and atypi- in cognitive therapy, 1 dropped out before the first