Posted by pseudoname on April 22, 2006, at 15:14:50
[Transcription by me of early trial of buprenorphine for depression, by HW Emrich in the UK journal "Lancet". Tables follow, transcribed to be viewed in a monospace font.]
Lancet. 1982 Sep 25; 2(8300): 709.
ANTIDEPRESSANT EFFECTS OF BUPRENORPHINE
Sir,–An antidepressant effect of opioids has been the subject of speculation since Emil Kraepelin's "opium cure". This therapy was never properly assessed. Fink's results with the partial opiate agonist cyclazocine [1] and the discovery of the endorphins reawakened interest in depression and opiate receptors. Open [2, 3] and double-blind [4] trials demonstrated an antidepressant effect of infusions of [beta]-endorphin. There are also hints from animal experiments [5] and from the effects of electroconvulsion therapy upon plasma [beta]-endorphin levels [6, 7] that activation of endorphinergic systems may be relevant to the antidepressant effects of ECT. This evidence prompted us to look for an opioid substance which easily penetrates the blood-brain barrier and has a low dependence liability. Buprenorphine meets these requirements. [8]
To investigate the antidepressant properties of this partial opiate we did a double-blind, placebo-controlled trial of ABA design (A = placebo; B = buprenorphine). The duration of the three phases varied in a randomised fashion between A1 (1-7 days), B (5-8 days), and A2 (0-4 days). The patients were not given conventional thymoleptic drugs. Before the trial there was a wash-out period of 4 days. During the buprenorphine treatment phase two sublingual tablets at 0.2 mg per day were given at 0830 and 1630 hours. Psychiatrists administered Hamilton scales every two days in the afternoons, together with a record of the global impression of depression, and a side effects scale [9] to record nausea, vomiting, dizziness, and euphoria. Thirteen patients who met Research Diagnostic Criteria for major depressive disorder gave their informed consent to the study. Most of the patients had been treated unsuccessfully by conventional thymoleptic drugs.
Four patients (see table) showed more than a 50% reduction in depression score when they had been on buprenorphine for 2-3 days; two patients showed a moderate response and four a slight reduction (p<0.02; Wilcoxon-test, two-tailed). Most patients experienced slight nausea, dizziness, and sedation (vomiting in one case); however, these side-effects, except for the vomiting, never become [sic] a problem.
This pilot study supports the view that activation of central opiate receptors may have a role in the drug treatment of endogenous depression, and suggests that buprenorphine could be an addition to the current arsenal of thymoleptic drugs.
We thank Dr S. D. Ashley and Dr J. M. Orwin (Reckitt and Colman, U.K.) for the buprenorphine; Dr A. König and Dr Ch. Schulz (Bezirkskrankenhaus Haar) for their contribution; and Mrs A. Wendl and the ward nurses. H. M. E. was supported by a grant of the Heisenberg-Programm of the Deutsche Forschungsgemeinschaft.
H. M. Emrich
P. Vogt
A. Herz
Max Planck Institute for Psychiatry,
D-8000 München 40, West GermanyW. Kissling
Psychiatric Clinic,
Technical University,
München1. Fink M, Simeon J, Itil TM, Freedman AH. Clinical antidepressant activity of cyclazocine: a narcotic antagonist. Clin Pharmacol Ther 1970; 11: 41-48.
2. Kline NS, Li Ch, Lehmann HE, Lajtha A, Laski E, Cooper T. [beta]-Endorphin-induced changes in schizophrenic and depressed patients. Arch Gen Psychiatry 1977; 34: 1111-1113.
3. Angst J, Autenrieth V, Brem F, Koukkou M, Meyer H, Stassen HH, Storck U. Preliminary results of treatment with [beta]-endorphin in depression. In: Usdin E, Bunney WE Jr, Kline NS, eds. Endorphins in mental health research. London: Macmillan, 1979: 518-28.
4. Gerner RH, Catlin DH, Gorelick DA, Hui KK, Li CH. [beta]-Endorphin. Intravenous infusion causes behavioural change in psychiatric inpatients. Arch Gen Psychiatry 1980; 37: 642-47.
5. Belenky GL, Holaday JW. The opiate antagonist naloxone modifies the effects of electroconvulsive shock (ECS) on respiration, blood pressure and heart rate. Brain Res 1979; 177: 414-17.
6. Emrich HM, Höllt V, Kissling W, Fischler M, Laspe H, Heinemann H, von Zerssen D, Herz A. [beta]-Endorphin-like immunoreactivity in cerbrospinal fluid and plasma of patients with schizophrenia and other neuropsychiatric disorders. Pharmakopsychiat 1979; 12: 269-76.
7. Inturrisi CE, Alexopoulos G, Lipman R, Foley K, Rossier J. [beta]-Endorphin immunoreactivity in the plasma of psychiatric patients receiving electroconvulsive treatment. Ann NY Acad Sci (in press) [1982; 398: 413-23].
8. Harcus AH, Ward AE, Smith DW. Buprenorphine in postoperative pain: results in 7500 patients. Anaesthesia 1980; 35: 382-86.
9. Emrich HM, Cording C, Pirée S, Kölling A, von Zerssen D, Herz A. Indication of an antipsychotic action of the opiate antagonist naloxone. Pharmakopsychiat 1977; 10: 265-70.
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EFFECT OF BUPRENORPHINE ON HAMILTON SCORES IN THIRTEEN DEPRESSED PATIENTS[Table. If viewed in a monotype font, columns will align.]
Pt age A1 B %
¯¯ ¯¯¯ ¯¯¯¯ ¯¯¯ ¯¯¯
1 F, 36 14.5 1.5 89.7
2 F, 42 44.5 11.0 75.3
3 F, 63 35.0 2.5 92.9
4 M, 31 23.5 12.0 48.9
5 M, 41 29.0 8.0 72.4
6 F, 40 21.0 28.5 -35.7
7 F, 68 20.7 18.5 10.6
8 F, 54 13.0 9.3 28.5
9 F, 58 25.0 20.7 17.2
10 F, 39 33.0 33.0 0.0
11 F, 29 38.3 38.5 -0.5
12 F, 44 27.5 23.8 13.5
13 F, 32 23.3 21.0 9.9
*A1 = averaged values of first placebo phase;
B = values of buprenorphine treatment phase after two days of treatment;
% = percentage change in ratings.
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EFFECT OF BUPRENORPHINE ON HAMILTON SCORES IN THIRTEEN DEPRESSED PATIENTS[Table. If viewed in a monotype font, headers & columns will align.]
Pt.......age........_A1_........__B_.......__%__
01........36........14.5........01.5........89.7
02........42........44.5........11.0........75.3
03........63........35.0........02.5........92.9
04........31........23.5........12.0........48.9
05........41........29.0........08.0........72.4
06........40........21.0........28.5........35.7-
07........68........20.7........18.5........10.6
08........54........13.0........09.3........28.5
09........58........25.0........20.7........17.2
10........39........33.0........33.0........00.0
11........29........38.3........38.5........00.5-
12........44........27.5........23.8........13.5
13........32........23.3........21.0........09.9Pt...age...._A1_....__B_....__%__
01____36____14.5____01.5____89.7
02____42____44.5____11.0____75.3
03____63____35.0____02.5____92.9
04____31____23.5____12.0____48.9
05____41____29.0____08.0____72.4
06____40____21.0____28.5____35.7-
07____68____20.7____18.5____10.6
08____54____13.0____09.3____28.5
09____58____25.0____20.7____17.2
10____39____33.0____33.0____00.0
11____29____38.3____38.5____00.5-
12____44____27.5____23.8____13.5
13____32____23.3____21.0____09.9
[Patients 4 & 5 were male; all others were female.]*A1 = averaged values of first placebo phase;
B = values of buprenorphine treatment phase after two days of treatment;
% = percentage change in ratings.
EFFECT OF BUPRENORPHINE ON HAMILTON SCORES IN THIRTEEN DEPRESSED PATIENTS
[Data transcribed from table]
1. F, age 36; A1: 14.5; B: 1.5; change: 89.7
2. F, age 42; A1: 44.5; B: 11.0; change: 75.3
3. F, age 63; A1: 35.0; B: 2.5; change: 92.9
4. M, age 31; A1: 23.5; B: 12.0; change: 48.9
5. M, age 41; A1: 29.0; B: 8.0; change: 72.4
6. F, age 40; A1: 21.0; B: 28.5; change: -35.7
7. F, age 68; A1: 20.7; B: 18.5; change: 10.6
8. F, age 54; A1: 13.0; B: 9.3; change: 28.5
9. F, age 58; A1: 25.0; B: 20.7; change: 17.2
10. F, age 39; A1: 33.0; B: 33.0; change: 0.0
11. F, age 29; A1: 38.3; B: 38.5; change: -0.5
12. F, age 44; A1: 27.5; B: 23.8; change: 13.5
13. F, age 32; A1: 23.3; B: 21.0; change: 9.9
*A1 = averaged values of first placebo phase;
B= values of buprenorphine treatment phase after two days of treatment;
[change] = percentage change in ratings.
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