Sertraline (Zoloft)

One of the SSRI anti-depressants, sertraline has become very popular. Like all SSRIs, it works as well as other anti-depressant for depression and much better than the others for obsessive-compulsive disorder. It has a long half-life of 26 hours, so can easily be taken as a single dose once a day. Like all SSRIs, it cannot be taken within a couple weeks of taking as MAO inhibitor anti-depressant. Sertraline has a high safety index.

Side-effects reported by over 4000 patients in initial clinical trials are listed by how much more often they occurred more than with placebo: nausea (14%), ejaculatory failure (13%), diarrhea/loose stools (11%), insomnia (10%), drowsiness (6%), tremor (6%), dry mouth (6%), decreased libido (5%), anorexia (5%), fatigue (4%), and sweating (4%). At 2%-3% were: constipation, dyspepsia, and agitation. Sexual side-effects may be much more common than suggested by the about, since roughly 70% of patients on SSRIs or venlafaxine report some difficulty in this area.

Sertraline = Imipramine for Panic and MDD in 26 week DB: In a DB study of 138 patients given sertraline 50-100mg/d vs. 69 given imipramine 100-200mg/d, MADRS depression score improvement was equal in both groups. CGI responder rate was 88% vs. 91% of completers. Dropouts due to side-effects were 11% for sertraline vs. 22% for imipramine, but bethanechol was not allowed in study. Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder. Lepola U, Arato M, Zhu Y, Austin C. Finland. J Clin Psychiatry. 2003 Jun;64(6):654-62.

Switch of Sertraline to Imipramine or Imipramine to Sertraline in Non-Responders Equally Effective: Many patients don't respond to the first anti-depressant on which they are tried. In a DB study, outpatients with chronic major depression, who failed to respond to 12 weeks of either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), in an earlier DB study were switched to 12 additional weeks of double-blind treatment with the alternate medication.  Dropouts due to side-effects were higher with imipramine, although bethanechol was not permitted in the study. While significantly more responded while on sertraline (60%)(163 mg/d average) than imipramine (46%)(221 mg/day average) in an intent-to-treat analysis, the difference disappeared when correcting for dropouts. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant non-responders and could be considered a standard of comparison for future studies. Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression. Thase ME, Rush AJ, Howland RH, Kornstein SG, Kocsis JH, Gelenberg AJ, Schatzberg AF, Koran LM, Keller MB, Russell JM, Hirschfeld RM, LaVange LM, Klein DN, Fawcett J, Harrison W.

Imipramine = Sertraline for Chronic Depression and Dysthymia; Personality Disorders Common But Make No Difference: In a DB study, 635 outpatients at 12 sites were treated for 12 weeks in a 2:1 ratio with sertraline 50-200 mg/day or imipramine 50-300. 52% achieved therapeutic response by 12 weeks with 21% succeeding after 8^th week. 12% discontinued due to imipramine side-effects vs. 6% due to sertraline. Martin Keller, U Brown, J Clin Psychiatry 55:598-607 11/98; Of responders, 60% achieved remission for both medications. J Affect Disord. 2001 Jun;65(1):27-36. A total of 46% of the patients had an axis II personality diagnosis, but improvement was similar whether there was such a diagnosis or not. Univ. Texas, Galvaston. Chronic depression and comorbid personality disorders: response to sertraline versus imipramine. Russell JM, Kornstein SG, Shea MT, McCullough JP, Harrison WM, Hirschfeld RM, Keller MB. J Clin Psychiatry. 2003 May;64(5):554-61

Imipramine = Sertraline in Elderly Depression: In a DB study of 55 elderly with Major Depression in an 8-week study, response rates were identical for both medicines even though dropouts due to side-effects were much higher for imipramine (150 mg/d) than for sertraline (50 mg/d) (46% vs. 30%). Bethanechol, which would have considerably decreased imipramine side-effects, was not used in the study. Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial. Forlenza OV, Almeida OP, Stoppe A Jr, Hirata ES, Ferreira RCR. Int Psychogeriatr. 2001 Mar;13(1):75-84

Imipramine = Sertraline in Chronic Dysthymia: In a DB PC study of 416 patients with early onset, chronic dysthymia (depression) for at least five years, imipramine and sertraline both did equally better than placebo although more patients stopped imipramine due to side-effects (18% vs. 6%). Bethanechol, which would have markedly reduced imipramine side-effects, was not permitted in the study. Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes. Kocsis JH, Zisook S, Davidson J, Shelton R, Yonkers K, Hellerstein DJ, Rosenbaum J, Halbreich U. Am J Psychiatry. 1997 Mar;154(3):390-5; also Arch Gen Psychiatry. 1996 Sep;53(9):777-8

Imipramine = Sertraline in Anger Attacks in Depressed: In a DB PC study of 162 patients with atypical depression or primary dysthymia, anger attacks decreased by 57% with imipramine, 53% with sertraline, and only 37% with placebo. A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia. Fava M, Nierenberg AA, Quitkin FM, Zisook S, Pearlstein T, Stone A, Rosenbaum JF. Psychopharmacol Bull. 1997;33(1):101-3

Depressed Women Did Better on SSRI Sertraline (Zoloft), Men Just as Well on Imipramine in Imperfect Study: A Spanish study of 239 adults with either Major Depression or Dysthymic Disorder, but not melancholic, were given either sertraline 50-200 mg/day or imipramine 75-225 mg/day in an open but randomized study. In women, 72% had a response improvement while on sertraline vs. 52% on imipramine. For men, 56% responded while on sertraline vs. 59% on imipramine. Dropouts were equal among men but higher on imipramine than sertraline for women (28% vs. 11%). Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders. Baca E, Garcia-Garcia M, Porras-Chavarino A. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):57-65. 

    Ed: Open trial studies are markedly inferior to double-blind studies. Psychiatrists have major, unfounded biases against older and less expensive tricyclic anti-depressants.  These biases can easily influence their ratings or be transmitted to patients. Also, probably due to ignorance, bethanechol was not used in this study and would have likely eliminated the high imipramine dropout rate.  Indeed, in every one of the six DB studies of imipramine vs. sertraline I have been able to find, covering 1643 patients, there was no difference in response rates. One other larger and DB study did find that premenopausal women did do better on sertraline, but that post-menopausal women did not and in all there was an equal response rate.  In every study, physicians were prohibited from using bethanechol, an extremely safe medication which would have markedly decreased imipramine side-effects. Of course, imipramine is an inexpensive generic and sertraline is a more expensive patented medication. For more, see Sertraline and Bethanechol.

Sertraline Helped Seasonal Affective Disorder: A DB PC study of 187 patients for 8 weeks found sertraline better than placebo. A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Moscovitch A, Blashko CA, Eagles JM, Darcourt G, Thompson C, Kasper S, Lane RM. Psychopharmacology (Berl). 2003 Sep 19

Elderly Barely Helped in DB: Huge 747 pt MDD DB PC. 45% sertraline vs. 35% placebo responded in 8 weeks. Decrease in HAM-D 7.4 vs. 6.6 placebo. USC. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KR, Shiovitz T, Weihs K; Sertraline Elderly Depression Study Group. Am J Psychiatry. 2003 Jul;160(7):1277-85

Post-Heart Attack and Angina Patients Helped in DB: One month after hospitalization for a heart attack or unstable angina, patients also suffering from major depression were treated in 369-patient DB PC study for 24 weeks. Sertraline was 50-200 mg/d. Patients on sertraline had a significant improvement in their self-reported quality of life.  Univ. Ottawa. Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome. Swenson JR, O'Connor CM, Barton D, Van Zyl LT, Swedberg K, Forman LM, Gaffney M, Glassman AH; Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Group. Am J Cardiol. 2003 Dec 1;92(11):1271-6. Ed: Fluoxetine is much cheaper and would probably work just as well, but fluoxetine does interact with quite a few other medicines.

Sertraline Barely Better Than Placebo for Kids: 376 youngsters ages 6 through 17 with major depression, DB PC. Sixty-nine percent of children who took Zoloft for 10 weeks showed a substantial reduction in symptoms, compared with 59 percent who took dummy pills. Christopher Varley a University of Washington 8/27/03 Journal of the American Medical Association. 

Sertraline Maintenance 88 weeks Helped: A 161-patient DB PC study of chronic major depression over 2 years or double depression rx up to 200 mg/d. All had responded in initial 12 weeks then randomized to placebo with taper 50 mg/wk. After 76 more weeks, 6% vs 23% had major depression recur, 26% v 50% had significant depressive symptoms. JAMA 11/18/98 280:1665

Sertraline = > Nortriptylinefor elderly depression: 208 >60yo MDD rx Nortrip 25-100 or sertraline 50-150mg/d. Response similar 60-70% by 12 weekds. Sertraline reported better on cognitive and energy. Funded by Pfizer. Bondareff, USC, AJP 00;157:729

Fluvoxamine Helped Elderly Depressed Better than Sertraline: In a 7-week DB study of 93 hospitalized depressed adults over age 59 with major depression, sertraline (150 mg daily) did not do as well as fluvoxamine (200 mg daily) with 56% improving while on sertraline vs.72% on fluvoxamine (P = 0.007). Since there was no placebo control group, one cannot conclude that sertraline was of any value. Sertraline Versus Fluvoxamine in the Treatment of Elderly Patients With Major Depression: A Double-blind, Randomized Trial. Rossini D, et al. University of Bologna, Italy. J Clin Psychopharmacol. 2005 Oct;25(5):471-475.

Sertraline Minimally Better than Placebo in Large DB of Elderly: 747 >60yo DB PC 8 weeks with HAMD >17 at start. Sertraline decreased 7.4 vs 6.6 point decrease for placebo! (Placebo had 89% of the benefit of the sertraline). An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KR, Shiovitz T, Weihs K. Am J Psychiatry. 2003 Jul;160(7):1277-85

Sertraline Helps AD Depression in Small DB: Arch Gen Psyc 7/03 Constantine Lyketsos, Johns Hopkins. DB PC 44 patients with Alzheimer’s depression rx 12 weeks. Depression helped but not memory.

Sertraline 50 = 150mg/d in 3 week Non-responders?: DB PC of 75 nonresponders after 3 weeks for 5 more weeks. The antidepressant effect of sertraline is not enhanced by dose titration: results from an outpatient clinical trial. However, after 8 week 57% 50mg and 79% 150 mg were responders but difference p<.10. U Penn: Schweizer E, Rynn M, Mandos LA, Demartinis N, Garcia-Espana F, Rickels K. Int Clin Psychopharmacol 2001 May;16(3):137-43. Similar findings comparing fluoxetine 20/d to 60/d. Psyc Drug Alerts 7/01 says similar lack of response to early dose escalation in paroxetine and maprotiline.

Sertraline May Lower Thyroxine: 11 hypothroid/thyroid cancer patients put on sertraline were later found to have increased thyrotropin and decreased leothyroxine of 11-50%. McCowen K, Spark R: Elevated serum thyrotropin in thyroxine-treated patients with hypothyroidism given sertraline (letter). NEJM 97;337:1010-1

Sertraline Rarely in Breast Milk: 24 of 25 infants reported in five studies had either low (7) or very low or non-detectable levelsof sertraline in plasma. One infant had a ligh level, i.e., one-half the mother’s level and in normal treatment range without any sign of harm to the infant. Wisner, AmJ Psychiatry 5/98;155:690.

Sertraline Bruxism Rx Buspirone: 4 cases of patients on 100-150mg/d. In first few weeks, tight and clenching jaw. 2 also severe headaches. . Bostwick, Mayo, J Clin Psych 99;60:857; similar reports with others SSRIs also responding to buspirone which doesn’t help if due to neuroleptics.

OK with Heart Disease: 556 pt hosp for MI or unstable angina in past 30 days. 2 week placebo. 369 DB PC 24 weeks.Sert 50mg/d titrated to max 200. Rate cardiovasc events same but less severe with sertraline (14.5% vs 22.4%). CGI-I better with sert but not HAM-D. Glassman, NYSPI, JAMA 02;288:701

Sertraline: sertraline inhibits platelet function to a greater extent than placebo even when given with aspirin or clopidogrel, according to the results of a randomized trial 8/26/03 Circulation. Victor L. Serebruany, MD, PhD, from Johns Hopkins Adding sertraline to other anticoagulants did not increase the risk of bleeding.