Studies completed at this institution strongly support the hypothesis that monoamine oxidase inhibitors, (MAOI) are superior to tricyclic antidepressants (TCA) and placebo to AD I (atypical depressives). These patients who meet RDC criteria for Major or Intermittent Depressive Disorder are also characterized by reactive mood, weight gain, oversleeping, rejection sensitivity, and lethargy. Post hoc it was observed that AD with a history of panic attacks (without agoraphobia) were least likely to respond to placebo and most likely to benefit from phenelzine, and this accounted for most of the drug vs. placebo variance. Another important unexpected observation was that imipramine, although less effective than phenelzine, is superior to placebo in AD. This suggests that current criteria for AD I include at least four distinct patients subtypes: MAOI responders (the largest group), TCA responders, placebo responders, and nonresponders. A pilot sleep study suggests AD I have the REM abnormality but not the sleep fragmentation observed in most depressives. Pilot data also suggest that patients with only some of the features of the AD syndrome (AD II) also have a superior improvement rate with phenelzine compared to TCA and placebo. We would like to repeat a double-blind trial of phenelzine, imipramine and placebo in AD I and AD II patients which will last 6 weeks for nonresponders and 12 weeks for responders. All patients will also have sleep polysomnographic studies and lactate infusions. Any single study does not prove a scientific fact or establish treatment efficacy. Repetition and extension of the original work will establish the selective utility of MAOI in this patient group. The health related and heuristic implications of this are obvious, and included more effective treatment for outpatient depressives and data supporting the validity of AD as a distinct depressive subtype. Replicating the import of a history of panic attacks will establish a simple clinical marker for identifying patients with antidepressant-sensitive diathesis in a heterogeneous depressed group previously considered """"""""neurotic"""""""" by many clinicians. Sleep polysomnographic findings and data from lactate infusions will be used to biologically characterize different types of AD patients (e.g. phenelzine responders, etc.). The work with AD II patients will help establish the boundaries of this syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH039143-03
Application #
3377119
Study Section
(TDAB)
Project Start
1984-03-01
Project End
1988-02-29
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Quitkin, Frederic M; McGrath, Patrick J; Stewart, Jonathan W et al. (2005) Remission rates with 3 consecutive antidepressant trials: effectiveness for depressed outpatients. J Clin Psychiatry 66:670-6
Quitkin, F M; McGrath, P J; Stewart, J W et al. (1998) Placebo run-in period in studies of depressive disorders. Clinical, heuristic and research implications. Br J Psychiatry 173:242-8
Quitkin, F M; McGrath, P J; Stewart, J W et al. (1996) Can the effects of antidepressants be observed in the first two weeks of treatment? Neuropsychopharmacology 15:390-4
Quitkin, F M; McGrath, P J; Stewart, J W et al. (1996) Chronological milestones to guide drug change. When should clinicians switch antidepressants? Arch Gen Psychiatry 53:785-92
McGrath, P J; Stewart, J W; Nunes, E V et al. (1993) A double-blind crossover trial of imipramine and phenelzine for outpatients with treatment-refractory depression. Am J Psychiatry 150:118-23
Quitkin, F M; Stewart, J W; McGrath, P J et al. (1993) Loss of drug effects during continuation therapy. Am J Psychiatry 150:562-5
Quitkin, F M; Stewart, J W; McGrath, P J et al. (1993) Further evidence that a placebo response to antidepressants can be identified. Am J Psychiatry 150:566-70
Stewart, J W; McGrath, P J; Rabkin, J G et al. (1993) Atypical depression. A valid clinical entity? Psychiatr Clin North Am 16:479-95
McGrath, P J; Stewart, J W; Tricamo, E et al. (1993) Paradoxical mood shifts to euthymia or hypomania upon withdrawal of antidepressant agents. J Clin Psychopharmacol 13:224-5
Stewart, J W; McGrath, P J; Quitkin, F M (1992) Can mildly depressed outpatients with atypical depression benefit from antidepressants? Am J Psychiatry 149:615-9

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