Correspondence BIOL PSYCHIATRY 1075 19~o;28:io65-- 1o8o Lithium Potentiation of Tetracyclic Antidepressants To the Editor: In some depressed patients, tricyclic antidepres- sants cannot be increased to effective doses because of peripheral anticholinergic side effects, the devel- opment of delirium, and so on. Recently, some stud- ies have suggested the efficacy of lithium added to tetracyclics for treatment of refractory depression. (Heninger et al 1983; Joice et ~ 1983; Kushnir 1986; Pai et al 1986; Price et al 1986; Weaver 1983). We consider the tetracyclic-I~thium combination to be potentially useful, as it tends to be less anticholinergic than most tricyclics and is more effective than tetra- cyclics alone. The present study reports on the results of lithium addition in 15 patients who had been on one tetracyclic for 3 weeks or more. The sample included ten in patients and five out- patients (eight male, seven female) of our university hospital, aged 35-63 years (mean -4- SD = 50.8 __. 9.5 years). All were free of major medical illness and met DSM-I~-R criteria for major depression without psychotic features. Among the 15 patients, 10 were melancholic and 6 had recurrent episodes (Table 1). Three tetracyclics were used: mianserin (seven pa- tients), teciptiline (a mianserin analog) (two patients), and maprotiline (six patients). The dosage and du- ration of treatment for each tetracyclic are shown in Table 1. The tetracyclics were gradually increased and fixed when the effect appeared to have reached its plateau. Once lithium was added, tetracyclics were continued in unchanged doses as a rule. As Price et al (1986) claimed that a 3-week trial is necessary to assess full benefit, we rated all patients on the 17- item Hamilton rating scale for depression, just before lithium addition and 1 and 3 weeks later. Following the criteria of de Montigny et al (1983), we defined responders as those whose Hamilton score decreased by more than 50%. Just before lithium addition, pa- tients had a mean (± $D) Hamilton score of 15.7 ± 5.3. After 1 and 3 weeks, it was 12.5 -4- 5.9 and 8.1 __ 4.5, respectively. There was a 48% decrease in Hamilton scores after 3 weeks (Student's t-test; p<0.001). Af- ter 1 week, three (20%) of the patients showed a response. Thereafter, two of them, however, showed a slight exacerbation (transient responder). After 3 weeks, a response was seen in eight patients (53%) (Table 1). The positive response rate was 78% for single and 50% for recurrent episodes, and 60% for melancholic and 80% for nonmelancholic patients, but the differences were not significant. With regard to adverse effects, xerostomia, con- stipation, dizziness, general fatigue, dysarthria, and finger tremor occurred before lithium addition. After lithium addition, nausea, blurred vision, and pares- thesia occurw/J (Table 2). These were, however, mild and well-tolerated. The lithium dose range (after 1 week) was 400-1200 mg/day (mean +-SD, 693 ---205 mg/day). The lithium concentration range (after 1 week) was 0.1-0.9 mEq/L (0.4? "--0.22 mEq/L) (Ta- ble 1). Lithium addition to tetracyclics had significant ef- fects on the Hamilton scores in the sample as a whole. Furthermore, no severe effects occurred throughout the treatment period. This study suggests that the tetracyclic-lithium combination is one of the useful methods for treatment of depression without severe adverse effects. T. Terao R. Yoshimura K. Abe Dep,'~nent of Psychiatry University of Occupational and Environmental Health School of Medicine Kitakyushu, 807, Japan References De Montigny C, Coumoyer G, Morissete R, Langlois R, Caill6 G (1983): Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression: Correla- tions with the neurobiologic actions of tricyclic anti- depressant drugs and lithium ion on the serotonin sys- tem. Arch Gen Psychia:ry 40:1327-1334. Heninger GR, Charney DS, Steinberg DE (1983): Lithium carbonate augmentationof antidepressanttreatment. Arch Gen Psychiatry 40:1335-1342. Joice PR, Hewland HR, Jones AV (1983): Rapid response to lithium in treatment resistant oepression. Br J Psy- chiatry 142:204-206. Kushnir SL (1986): Lithium-antidepressant combinations in the treatment of depressed, physically ill geriatric pa- tients. Am J Psychiatry 143:378-379.