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Prophylactic Lithium Carbonate With and Without Imipramine for Bipolar 1 Patients: Title and subTitle BreakA Double-blind Study

Frederic M. Quitkin, MD; John Kane, MD; Arthur Rifkin, MD; J. R. Ramos-Lorenzi, MD; D. V. Nayak, MD
[+] Author Affiliations

Accepted for publication Jan 22, 1981.

Reprint requests to New York State Psychiatric Institute, 722 W 168th St, New York, NY 10032 (Dr Quitkin).


Arch Gen Psychiatry. 1981;38(8):902-907. doi:10.1001/archpsyc.1981.01780330060006
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• The efficacy of lithium carbonate plus imipramine hydrochloride vs lithium carbonate plus placebo in preventing relapse was assessed in a prospective, hydro- doubleblind study of 75 bipolar 1 patients. Outcome measures included type of relapse, time until relapse, and subsequent illness course. Infrequent depressive relapse in either treatment group precluded any demonstration of an advantage of adding imipramine to a lithium carbonate regimen. There was little evidence that the combination of lithium carbonate and imipramine caused adverse reactions. However, interactions between type of most recent episode, treatment condition, sex, and type of relapse showed that women and mania-prone patients treated with imipramine had an increased risk of mania. Life table analysis showed that the overall probability of remaining well was the same for both treatment groups and that two thirds of all relapses occurred in the first six months.

REFERENCES

Baastrup PC, Poulsen JC, Schou M, et al:  Prophylactic lithium: Double-blind discontinuation in manic-depressive and recurrent depressive disorders . Lancet 1970;;2:326-330.
Melia PI:  Prophylactic lithium: A double-blind trial in recurrent affective disorders . Br J Psychiatry 1970;;116:621-624.
Coppen A, Noguera R, Bailey J, et al:  Prophylactic lithium in affective disorders . Lancet 1971;;2:275-279.
Hullin RP, McDonald R, Allsop MNE:  Prophylactic lithium in recurrent affective disorders . Lancet 1972;;1:1044-1046.
Cundall RL, Brooks PW, Murray LG:  A controlled evaluation of lithium prophylaxis in affective disorders . Psychol Med 1972;;2:308-311.
Prien RF, Caffey EM Jr, Klett CJ:  Prophylactic efficacy of lithium carbonate in manic-depressive illness: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group . Arch Gen Psychiatry 1973;;28:337-341.
Prien RF, Klett CJ, Caffey EM Jr:  Lithium carbonate and imipramine in the prevention of affective episodes: A comparison of recurrent affective illness . Arch Gen Psychiatry 1973;;29:420-425.
Stallone F, Shelly E, Mendlewicz J, et al:  The use of lithium in affective disorders: III. A double-blind study in prophylaxis in bipolar illness . Am J Psychiatry 1973;;130:1006-1010.
Fieve R, Kumbaraci T, Dunner D:  Lithium prophylaxis of depression in bipolar I and bipolar II and unipolar patients . Am J Psychiatry 1976;;133:925-926.
Bunney WE Jr:  Psychopharmacology of the switch process in affective disorders , in Lipton MA, DiMascio A, Killiam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978;, pp 1249-1259.
Wehr TA, Goodwin FK:  Rapid cycling in manic-depressives induced by tricyclic antidepressants . Arch Gen Psychiatry 1979;;36:555-559.
Lundquist G:  Prognosis and course in manic-depressive psychoses . Acta Psychiatr Scand , (suppl 35) , 1945;, pp 5-96.
Perris C:  The course of depressive psychoses . Acta Psychiatr Scand , (suppl 194) , 1966;, pp 1-188.
Prien RF, Caffey EM Jr, Klett CJ:  Factors associated with treatment success in lithium carbonate prophylaxis: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group . Arch Gen Psychiatry 1974;;31:189-192.
Spitzer RL, Endicott J, Robins E:  Research Diagnostic Criteria: Rationale and reliability . Arch Gen Psychiatry 1978;;35:773-782.
Fleiss J, Dunner DL, Stallone F, et al:  The life table: A method for analyzing longitudinal studies . Arch Gen Psychiatry 1976;;33:107-112.
Mantel M:  Evaluation of survival data and two new rank order statistics arising in its consideration . Cancer Chemother Rep 1966;;50:163-170.
Cohen J: Statistical Power Analysis for the Behavioral Sciences . New York, Academic Press Inc, 1969;, pp 174-208.
Hestbech J, Hansen IT, Amdisen A, et al:  Chronic renal lesions following long-term treatment with lithium . Kidney Int 1977;;12:205-213.
Rennie T:  Prognosis in manic-depressive psychoses . Am J Psychiatry 1942;;98:801-814.
Bratfos O, Haug J:  Course of manic-depressive psychoses: A follow-up investigation of 215 patients . Acta Psychiatr Scand 1968;;44:89-112.
Court JH:  The continuum model as a resolution of paradoxes in manic depressive psychoses . Br J Psychiatry 1972;;120:133-141.
Prange AJ:  The use of drugs in depression: Its theoretical and practical implications . Psychiatr Ann 1973;;3:56-73.
Quitkin F, Rifkin A, Kane J, et al:  Amine biochemistry and treatment of depression , in Klein DF, Gittelman-Klein R (eds): Progress in Psychiatric Drug Treatment . New York, Brunner/Mazel Inc, 1976;, pp 79-86.
Klein DF:  Psychotropic drugs and the regulation of behavioral activation in psychiatric illness , in Smith CC (ed): Drugs and Cerebral Function . Springfield, Ill, Charles C Thomas Publisher, 1970;, pp 69-81.
Klein DF, Gittelman R, Quitkin FM, et al: Diagnosis and Drug Treatment of Psychiatric Disorders , ed 2. Baltimore, Williams & Wilkins Co, 1980;.

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Baastrup PC, Poulsen JC, Schou M, et al:  Prophylactic lithium: Double-blind discontinuation in manic-depressive and recurrent depressive disorders . Lancet 1970;;2:326-330.
Melia PI:  Prophylactic lithium: A double-blind trial in recurrent affective disorders . Br J Psychiatry 1970;;116:621-624.
Coppen A, Noguera R, Bailey J, et al:  Prophylactic lithium in affective disorders . Lancet 1971;;2:275-279.
Hullin RP, McDonald R, Allsop MNE:  Prophylactic lithium in recurrent affective disorders . Lancet 1972;;1:1044-1046.
Cundall RL, Brooks PW, Murray LG:  A controlled evaluation of lithium prophylaxis in affective disorders . Psychol Med 1972;;2:308-311.
Prien RF, Caffey EM Jr, Klett CJ:  Prophylactic efficacy of lithium carbonate in manic-depressive illness: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group . Arch Gen Psychiatry 1973;;28:337-341.
Prien RF, Klett CJ, Caffey EM Jr:  Lithium carbonate and imipramine in the prevention of affective episodes: A comparison of recurrent affective illness . Arch Gen Psychiatry 1973;;29:420-425.
Stallone F, Shelly E, Mendlewicz J, et al:  The use of lithium in affective disorders: III. A double-blind study in prophylaxis in bipolar illness . Am J Psychiatry 1973;;130:1006-1010.
Fieve R, Kumbaraci T, Dunner D:  Lithium prophylaxis of depression in bipolar I and bipolar II and unipolar patients . Am J Psychiatry 1976;;133:925-926.
Bunney WE Jr:  Psychopharmacology of the switch process in affective disorders , in Lipton MA, DiMascio A, Killiam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978;, pp 1249-1259.
Wehr TA, Goodwin FK:  Rapid cycling in manic-depressives induced by tricyclic antidepressants . Arch Gen Psychiatry 1979;;36:555-559.
Lundquist G:  Prognosis and course in manic-depressive psychoses . Acta Psychiatr Scand , (suppl 35) , 1945;, pp 5-96.
Perris C:  The course of depressive psychoses . Acta Psychiatr Scand , (suppl 194) , 1966;, pp 1-188.
Prien RF, Caffey EM Jr, Klett CJ:  Factors associated with treatment success in lithium carbonate prophylaxis: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group . Arch Gen Psychiatry 1974;;31:189-192.
Spitzer RL, Endicott J, Robins E:  Research Diagnostic Criteria: Rationale and reliability . Arch Gen Psychiatry 1978;;35:773-782.
Fleiss J, Dunner DL, Stallone F, et al:  The life table: A method for analyzing longitudinal studies . Arch Gen Psychiatry 1976;;33:107-112.
Mantel M:  Evaluation of survival data and two new rank order statistics arising in its consideration . Cancer Chemother Rep 1966;;50:163-170.
Cohen J: Statistical Power Analysis for the Behavioral Sciences . New York, Academic Press Inc, 1969;, pp 174-208.
Hestbech J, Hansen IT, Amdisen A, et al:  Chronic renal lesions following long-term treatment with lithium . Kidney Int 1977;;12:205-213.
Rennie T:  Prognosis in manic-depressive psychoses . Am J Psychiatry 1942;;98:801-814.
Bratfos O, Haug J:  Course of manic-depressive psychoses: A follow-up investigation of 215 patients . Acta Psychiatr Scand 1968;;44:89-112.
Court JH:  The continuum model as a resolution of paradoxes in manic depressive psychoses . Br J Psychiatry 1972;;120:133-141.
Prange AJ:  The use of drugs in depression: Its theoretical and practical implications . Psychiatr Ann 1973;;3:56-73.
Quitkin F, Rifkin A, Kane J, et al:  Amine biochemistry and treatment of depression , in Klein DF, Gittelman-Klein R (eds): Progress in Psychiatric Drug Treatment . New York, Brunner/Mazel Inc, 1976;, pp 79-86.
Klein DF:  Psychotropic drugs and the regulation of behavioral activation in psychiatric illness , in Smith CC (ed): Drugs and Cerebral Function . Springfield, Ill, Charles C Thomas Publisher, 1970;, pp 69-81.
Klein DF, Gittelman R, Quitkin FM, et al: Diagnosis and Drug Treatment of Psychiatric Disorders , ed 2. Baltimore, Williams & Wilkins Co, 1980;.

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