Imipramine
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Imipramine

Imipramine is the best researched of all anti-depressant medications.  It is available as an inexpensive generic, costing the pharmacist roughly $5 for the typical one month’s supply.  It works as well or better than all other anti-depressants although certain patients may do better on other medications.  It does cause dry mouth and other anti-cholinergic side-effects in perhaps 25% of patients. This side-effect is easily treated with bethanechol.  Unfortunately, in 12 years thanks to poor governmental regulation of greedy drug companies, the cost of generic bethanechol has skyrocketed from $4 for a bottle of one hundred 25mg tablets to at least $150 in the U.S.  The least expensive bethanechol I have found are 50 mg tablets from Canada or England via the internet. These can easily be broken in half, providing a 25 mg dose for 31 cents. Since only 25% of patients will need these and very few will need over three doses a day, the total cost is still far below all brand name anti-depressants.

The major drug companies would have you believe that no one prescribes imipramine any more or even that it is unethical to use imipramine, or any other low cost generic medication for that matter. Since the manufacturers can’t get away with claiming that their brand name anti-depressants are any better, they try to claim that the side-effects of generic medications are just too terrible. Of course, they were peddling these very same terrible medications as wonder drugs just one or two decades ago when they still enjoyed patent protection. In fact, major researchers at some major universities still use imipramine in many studies. The University of Pittsburgh, Case Western University, and the New York State Psychiatric Institute have all published studies using imipramine as the primary medication for depression or agoraphobia in 2002, as did many major research centers in other countries.

The speed and effectiveness of imipramine can be boosted in patients requiring more rapid action by adding thyroid medication as described under that section below.

There are some patients who should not use imipramine as their first choice. While research has documented that patients on imipramine live longer thanks to having fewer heart attacks, it is now discouraged for heart disease patients by at least some authors on theoretical grounds. Alternative anti-depressants, like fluoxetine, trazodone, bupropion, and venlafaxine, are thought to also have a beneficial effect on suppressing heart attacks with less chance of causing heart problems. Hypericum (St. John’s wort) also has no harmful effect on ECG and appears safe.

Also, patients with bipolar depression should first be tried on bupropion, fluoxetine, or another SSRI, since these are less likely to cause a switch into mania. However, it is noteworthy that adding thyroxine to imipramine reduces such rapid cycling. It is not known whether this would decrease the risk of a manic switch down to the levels of bupropion or the SSRIs. Thus, imipramine is probably still an acceptable back-up for bipolar depressed patients when other medicines and approaches aren’t working.

Another group probably better treated with fluoxetine, trazodone, bupropion, or venlafaxzine are diabetics. Tricyclics, including imipramine, tends to worsen their blood glucose control, while some of the others improve it.

Imipramine is usually best taken as a single dose at bedtime. For most patients, a low dose of 100 mg a night is adequate. Severely depressed hospitalized patients are more commonly treated with 150 to 300 mg per day. For patients taking these higher doses, getting a single blood level after one week at a stable dose can help detect cases where the blood levels might be so high as to require decrease to avoid a risk of serious side-effects. Studies show that imipramine is actually better than SSRIs for the very severely depressed and it is recommended as a frontline medication for the psychotically depressed in the Texas Depression Treatment Algorithm. Research also shows that there is no value to adding anti-psychotics when treating psychotically depressed patients, at least when the psychosis is "mood congruent," for example the patient who is so depressed he thinks he is dying of cancer.

Imipramine Better than Sertraline in Men, Opposite for Women: 635 21-65yo pt MDD or dysthymia DB 12 weeks. Both started at 50mg/d  of sertraline or imipramine up to 300 and set up to 200 as needed. Women response 57% sertraline vs. 46% imipramine and fewer drop outs with sertraline. Men 62% responded to imipramine vs. 45% to sertraline and fewer drop-outs with imipramine. Kornstein, AJP 00;157:1445, Med College of Virginia.

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 8th 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.

Imipramine Helps Depression in Opiate Addicts: 12 week DB placebo 137 pt 57% responders vs 7% placebo. Big effect. Some decr in use and craving tho few achieved abstinence. Ed Nunes, Columbia, Arch Gen Psychiatry ’98;55:153-160.

Bright Light Did Better than Imipramine for Non-Seasonal Depression: Short 3 wk small 34 pt inpatient study randomized DB PC 5000 lux 6-8 am without or without imipramine 150/d or 500 lux with 150mg imipramine. No difference although bright light alone non-significantly better. Prague, Bright light therapy and/or imipramine for inpatients with recurrent non-seasonal depression. Prasko J, Horacek J, Klaschka J, Kosova J, Ondrackova I, Sipek J. Ed: The study is just too short and too small to suggest any conclusion at all.

Imipramine = Amisulpride: DB PC 6 months dysthymia or MDD. Amisulpride (selective antagonist of D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses) 50/d or imipramine 100/d. More side-effects with imipramine with anti-cholinergic singled out. Hopital Salpetriere, Paris. Amisulpride versus imipramine and placebo in dysthymia and major depression. Amisulpride Study Group. Lecrubier Y, Boyer P, Turjanski S, Rein W. J Affect Disord 1997 Apr;43(2):95-103 J Affect Disord 1997 Apr;43(2):95-103

Imipramine = Amitriptyline = Moclobemide = Oxaprotiline; Two Week Improvement Predicts Response: Two DB PC studies 1706 patients added together. amitriptyline (N = 120), oxaprotiline (N = 120), imipramine (N = 506) and moclobemide (N = 580) with placebo (N = 189/+191). No difference between drugs in onset of action. Patients showing improvement in first 14 days much more likely to be responders. Only 20-25% of all patients true med responders. Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Stassen HH, Angst J, Delini-Stula A. Zurich: Pharmacopsychiatry 1996 May;29(3):87-96

Imipramine Better than Buspirone Which was Better than Placebo for Elderly Depressed: DB PC 8 weeks 177 unipolar MDD >65yo. 77% imipramine, 61% buspirone, 42% placebo responded. U Penn. Buspirone and imipramine for the treatment of major depression in the elderly. U Penn, Schweizer E, Rickels K, Hassman H, Garcia-Espana F. J Clin Psychiatry 1998 Apr;59(4):175-83

Imipramine = Citalopram: DB 472 MDD 6 week with optional 22 add-on. Anti-depressant benefit equal tho more side-effects, primarily anti-cholinergic, with imipramine. Citalopram and imipramine in the treatment of depressive patients in general practice. A Nordic multicentre clinical study. Rosenberg C, Damsbo N, Fuglum E, Jacobsen LV, Horsgard S. Int Clin Psychopharmacol 1994 Mar;9 Suppl 1:41-8

Tricyclics = Fluoxetine and Help Suicidal Ideation: Double-blind, controlled clinical trial data were evaluated to assess a hypothetical relationship between fluoxetine and suicidality (suicidal acts and ideation) in patients with mood (n = 5,655) and nonmood disorders (n = 4,959) (Mantel-Haenszel incidence difference method). In mood disorders, act rates (suicide attempts/completions) were low (treatment differences nonsignificant). Substantial suicidal ideation emerged less frequently with fluoxetine than placebo and was comparable with fluoxetine and tricyclic antidepressants. Improvement in ideation was greater with fluoxetine than placebo; it was comparable with fluoxetine and tricyclic antidepressants (United States trials) and greater with tricyclic antidepressants than fluoxetine (international trials). In nonmood disorders, no suicides occurred. Act and emergent ideation rates were low (treatment differences nonsignificant). Evaluation of suicidality during pharmacologic treatment of mood and nonmood disorders. Tollefson GD, Fawcett J, Winokur G, Beasley CM Jr, Potvin JH, Faries DE, Rampey AH Jr, Sayler ME. Ann Clin Psychiatry 1993 Dec;5(4):209-24

Fluvoxamine Did Better than Imipramine: 338 MDD DB PC in North America. Imipramine not significantly better than placebo. Imipramine side-effect of dry mouth singled out, fluvoxamine nausea and vomiting. Antidepressant efficacy in relation to item analysis and severity of depression: a placebo-controlled trial of fluvoxamine versus imipramine. U Vienna, Kasper S, Moller HJ, Montgomery SA, Zondag E. Int Clin Psychopharmacol 1995 Jan;9 Suppl 4:3-12

Imipramine DId Better than Fluvoxamine for Panic: 148 pt DBPC 8 weeks. Imipramine average dose 165mg/d vs fluvoxamine 171mg/d. Panic attacks decreased by 6.0/week for imipramine vs. 3.3 for fluvoxamine. No difference in med dropouts from side-effects. Comparison of fluvoxamine, imipramine, and placebo in the treatment of outpatients with panic disorder. Nair NP, Bakish D, Saxena B, Amin M, Schwartz G, West TE. Anxiety 1996;2(4):192-8

Imipramine = Fluvoxamine: 150 DB PC 6 week MDD. Fluvoxamine 50-150 vs. imipramine 80-240. No difference in efficacy. Anti-cholinergic specifically mentioned (dry mouth, dizziness, urinary retention) and dry mouth said not to be transient. Fluvoxamine caused nausea and ejaculatory difficulty which was not transient. Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients. Claghorn JL, Earl CQ, Walczak DD, Stoner KA, Wong LF, Kanter D, Houser VP. J Clin Psychopharmacol 1996 Apr;16(2):113-20

Imipramine = Fluvoxamine: 151 DB 4 week MDD. 67% decrease HAM-D fluvoxamine, 62% decrease imipramine. Dizziness and orthostatic hypotension imipramine difficulty. Fluvoxamine to 300mg/d, imipramine up to 200 mg/d. A double-blind controlled clinical trial comparing fluvoxamine with imipramine. Guelfi JD, Dreyfus JF, Pichot P. Br J Clin Pharmacol 1983;15 Suppl 3:411S-417S

Imipramine = Fluoxetine for Atypical Depression Temprament: 154 MDD DB PC with atypical depression with Columbia criteria given Temprament and Character Inventory. 10 week study found improved depression and character traits, e.g. self-directedness and harm avoidance. Comparison of the effects of fluoxetine, imipramine and placebo on personality in atypical depression. Agosti V, McGrath PJ. J Affect Disord 2002 Sep;71(1-3):113-20; NYSPI

Lilly Says Fluoxetine = Imipramine but Huge Imipramine Dropout: DB MDD 124 pt with "agitate depression" rx fluoxetine vs imipramine with 43% imipramine dropout vs 10% fluoxetine. Agitated patients, like other patients, did better on fluoxetine due to high imipramine dropout. Says 24% of imipramine side-effects CNS ones. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. Lilly Labs Indianapolis. Tollefson GD, Greist JH, Jefferson JW, Heiligenstein JH, Sayler ME, Tollefson SL, Koback K. J Clin Psychopharmacol 1994 Dec;14(6):385-91

Fluoxetine + a Tricyclic was Faster and Better: Combination of fluoxetine (an SSRI) with desipramine or other TCAs produces a faster and more robust antidepressant response than either alone. Nelson JC, Mazure CM, Bowers MB Jr, Jatlow PI. A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. [see comments.]. Arch Gen Psychiatry. 1991;48:303-307. Seth R, Jennings AL, Bindman J, Phillips J, Bergmann K. Combination treatment with noradrenalin and serotonin reuptake inhibitors in resistant depression. Br J Psychiatry. 1992;161:562-565.

Imipramine = Fluoxetine: 198 pt MDD DB PC. No difference between meds tho favors imipramine. More imipramine side-effects noted. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. Feighner JP, Boyer WF, Merideth CH, Hendrickson GG. Int Clin Psychopharmacol 1989 Apr;4(2):127-34

Imipramine = Imipramine & Lithium: Lack of advantage for imipramine combined with lithium versus imipramine alone in the treatment of major depression--a double-blind controlled study. Israel: Shahal B, Piel E, Mecz L, Kremer I, Klein E. Biol Psychiatry 1996 Dec 1;40(11):1181-3

Imipramine > Mirtazapine: DB 107 severe depressed rx to preset blood levels. 4 weeks. 50% vs 22% response rate. A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients. Bruijn JA, Moleman P, Mulder PG, van den Broek WW, van Hulst AM, van der Mast RC, van de Wetering BJ. Psychopharmacology (Berl) 1996 Oct;127(3):231-7

Imipramine-Lithium Better than Mirtazapine-Lithium: 100 inpt DB PC imipramine or mirtazapine. Those not responding after 4 weeks (mirtazapine 35, imipramine 22) had lithium added to 0.5-1.0mmol/L. 36% mirtazapine-lithium 48% v 52% imipramine-lithium 64% responded. Five imipramine dropouts due to severe side-effects but percentages are intent to treat. Comparison of 2 treatment strategies for depressed inpatients: imipramine and lithium addition or mirtazapine and lithium addition. Bruijn JA, Moleman P, Mulder PG, van den Broek WW., J Clin Psych 98;59:657

Imipramine = Nefazodone: DB PC 123 pt 8 weeks. Equal response tho author tries to say nefazodone did better based on very small percentage difference. More imipramine side-effect dropouts stressed by author. Cohn Center. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. Cohn CK, Robinson DS, Roberts DL, Schwiderski UE, O'Brien K, Ieni JR. J Clin Psychiatry 1996;57 Suppl 2:15-8

Imipramine = Nefazodone in 6 Studies: Meta-analysis of 6 DB PC studies 345 placebo pt, 288 imipramine, 184 nefazodone pt found equal benefit. However, authors tease out two HAM-D items in which nafazodone at some point did better. They note the greater imipramine drop out rate of 17% vs 5% for nefazodone or placebo. Response of anxiety and agitation symptoms during nefazodone treatment of major depression. Rush-Presbyterian: Fawcett J, Marcus RN, Anton SF, O'Brien K, Schwiderski U. J Clin Psychiatry 1995;56 Suppl 6:37-42

Imipramine = Nefazodone at U Penn: DB PC 283 MDD 8 weeks. Nefazodone better tolerated. Nefazodone and imipramine in major depression: a placebo-controlled trial. Rickels K, Schweizer E, Clary C, Fox I, Weise C. Br J Psychiatry 1994 Jun;164(6):802-5

Imipramine/Paroxetine Combo Helped only Low Lithium Bipolar Depression: DB PC 117 bipolar depressed on lithium. Some also on valproic or carbamazepine. Only those on lithium under 0.8 mEq/L helped by anti-depressant. Nemerodd C et al: Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Amer J Psyc 01;158:906-12. Emory U & GlaxoSmithKline

Paroxetine Better than Imipramine for Teen Depression: 275 MDD teens 8 wk DB PC paroxetine 20-40/d, imipramine 200-300/d. Paroxetine lowered HAM-D but no better than placebo on parent or self rating. Imipramine no better on anything. Imipramine dropout incredibly high 31% vs 10% paroxetine and 6% placebo. High side-effects cardiac. Brown Univ. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP. J Am Acad Child Adolesc Psychiatry 2001 Jul;40(7):762-72

Imipramine = Paroxetine in Maintenance: DB PC 734 pt 6 week with 219 responders in DB PC 1 year f/u. Equal efficacy but says higher imipramine dropout and paroxetine favored by researchers. A double-blind comparison of paroxetine with imipramine in the long-term treatment of depression. Houston: Claghorn JL, Feighner JP. J Clin Psychopharmacol 1993 Dec;13(6 Suppl 2):23S-27S

Imipramine = Paroxetine for Elderly Depression: 198 MDD >60yo DB imipramine 50-100/d vs paroxetine 20-40/d. No difference in depression or frequency of side-effects but abstracts singles out anti-cholinergic (13% vs 6%) and serious side-effects (8% vs 4%) as more common with imipramine. A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia. Katona CL, Hunter BN, Bray J. Int J Geriatr Psychiatry 1998 Feb;13(2):100-8

Imipramine = Paroxetine in Chinese Depression: 40 pt MDD DB. 6 weeks. Imipramine 100mg vs paroxetine 20-30/d. Response rate 65% vs. 67%. Authors say paroxetine better because fewer side-effects. Taipei. Paroxetine in the treatment of Chinese patients with depressive episode: a double-blind randomized comparison with imipramine. Chiu HJ, Hong CJ, Chan CH. Zhonghua Yi Xue Za Zhi (Taipei) 1996 Jun;57(6):418-23

Reboxetine = Imipramine and Both Better than Fluoxetine: 1144 major depr pt DB PC rebox 8-10mg/d, fluo 20-40mg/d, imip 150-200mg/d. 8 wk. More S-E with imip. Massana, Barcelona, APA 5/30/98 Toronto

Reboxetine = Imipramine: DB 256 pt 6 weeks. Reboxetine is a selective NE reuptake inhibitor. Equal efficacy but more side-effects with imipramine with anti-cholinergic singled out. Freie Univ, Berlin. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes. Berzewski H, Van Moffaert M, Gagiano CA Eur Neuropsychopharmacol 1997 Apr;7 Suppl 1:S37-47; discussion S71-3.

SAMe IM = Imipramine: DB 293 pt MDD 4 weeks. SAMe 400mg/d im vs imipramine 150mg/d. Both equal decrease in HAM-D. Side-effects slightly less with SAMe. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Pancheri P, Scapicchio P, Chiaie RD. Rome, La Spienza, Italy. Int J Neuropsychopharmacol 2002 Dec;5(4):287-94

SAMe IM or P.O. = Imipramine:DB 295 pt MDD in 4 week IM study and DB 281 pt MDD in 6 week 1600mg/d SAMe p.o. study both with imipramine 150 mg/d. No difference in efficacy. SAMe well tolerated and fewer side-effects. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Delle Chiaie R, Pancheri P, Scapicchio P. Am J Clin Nutr 2002 Nov;76(5):1172S-6S

SAMe + Imipramine Faster than Imipramine in DB: 40 pt DB PC imipramine 150/d with or without SAMe 200mg IM. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Psychiatry Res 1992 Dec;44(3):257-62

Imipramine = Sertraline for Dysthymia in DB: 410 pt dysthymia >5 yr, most since age 12 for an average of 30 years! Half ad had episode MDD and half substance abuse. DB PC imipramine up to 300/d, sertraline up to 200/d 12 weeks. Responses in 64% imipramine, 59% sertraline, 44% placebo. Kocsis J et al: Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes. Amer J Psyc 97;154:390-5; Same study?: 416 pt dysthymia. A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia. "The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication." Thase ME, Fava M, Halbreich U, Kocsis JH, Koran L, Davidson J, Rosenbaum J, Harrison W. Arch Gen Psychiatry 1996 Sep;53(9):777-84

Imipramine = Sertraline for Older Adults: 55 older adults DB 50mg sertraline or 150 mg/d imipramine. 8 weeks. Response rate equal, but more dropouts with imipramine. 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; Dr. Forlenza confirmed via email 1/14/03 that bethanechol not used and gave as the reason "in order not to complicate the double-blind design."

Imipramine = Sertraline in Maintenance of Improvement: 635 chronic MDD x 2 yr or dysthymia + MDD DB sertraline or imipramine x 12 week. Non-responders switched to opposite. Responders from either study put in second maintenance 18 week study. 60% went into remission and 40% partial remission for each med. No difference in dropouts in maintenance phase. Stanford Univ., Sertraline versus imipramine to prevent relapse in chronic depression. Koran LM, Gelenberg AJ, Kornstein SG, Howland RH, Friedman RA, DeBattista C, Klein D, Kocsis JH, Schatzberg AF, Thase ME, Rush AJ, Hirschfeld RM, LaVange LM, Keller MB. J Affect Disord 2001 Jun;65(1):27-36; Thase responded in regards to his report on the same trial in the Arch Gen Psych 3/02 that bethanechol was not used because, "sedative-hypnotic medications are not permitted in many trials even though the SSRIs are generally worse than the TCAs in this regard. generally adjunctives are limited to nonpsychotropics (e.g., laxatives, artificial tears) to prevent contamination of the clinical trial." 1/13/03 email.

Imipramine = Sertraline for Dysthymia: 419 pt with 5+ year hx of dysthymia without MDD rx 12 weeks DB PC. Both treatments superior to placebo and equal. Dropouts due to side-effects 18% vs 6%. No mention of bethanechol. Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes. Cornell: 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

Imipramine = Sertraline for Anger Attacks in Atypical Depression or Dysthymia: DB PC 168 pt. Anger attacks decreased 57%, 53%, and only 37% with placebo although the difference not quite statistically significant. A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia. MGH: Fava M, Nierenberg AA, Quitkin FM, Zisook S, Pearlstein T, Stone A, Rosenbaum JF. Psychopharmacol Bull 1997;33(1):101-3

Imipramine = < Sertraline for Schiz Depression: DB 40 pt 5 week sertraline 50/d vs imipramine 150/d. Equally effective, but sertraline faster with fewer side-effects. No mention is bethanechol was permitted or used. A comparative study of sertraline versus imipramine in postpsychotic depressive disorder of schizophrenia. Kirli S, Caliskan M. Schizophr Res 1998 Sep 7;33(1-2):103-11

St. John’s Wort = 150mg Imipramine: DB 150 imip vs 250mg hypericum extract BID St John’s 6 weeks 324 pts mild-mod depr found no diff. Side-effects 39% St. John vs. 63% imip and 3% vs 16% drop-out due to s-e. BMJ 2000 Sep 2;321(7260):536-9. Notes also used for anxiety in Europe.

St. John’s Wort Helps Severe Depr = Imip: DB PC 6 wk 1800 mg/d extract LI 160 vs imipramine found both equally effective with HAM-D 25.3-15.6 for St John’s and 26.1-14.5 for imipramine. Fewer S-E with St. John’s. Vorbach, Darmstadt. Pharmacopsychiatry 9/97;30 Suppl 2:81. Refers to several earlier DB studies where successful.

St. John’s Wort = Imipramine 100mg: DB PC 263 pt with moderate depression rx 350mg tid vs imipramine 50-25-25. More side-effects with imipramine and no mention of bethanechol in article itself. By far most common imipramine side-effect was dry mouth at 38% with only 46% of imipramine patients reporting some side-effect (hypericum 22% and placebo 19%)(nausea second most common at 11% imipramine and 8% hypericum; only significant difference 6% imipramine dizzy vs 1% hypericum). No serious side-effect tho one placebo patient attempted suicide. 1% imipramine dropout. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. Philipp M, Kohnen R, Hiller KO. BMJ 1999 Dec 11;319(7224):1534-8, Bezirkskrankenhaus, Landshut, Germany

St. John’s = Imipramine in Severe Depression: DB 1800mg/d hypericum vs imipramine 150mg/d in 6 week study of severe depression. Both groups showed equal improvement. Germany. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Side-effects worse with imipramine, tho no mention of bethanechol. Vorbach EU, Arnoldt KH, Hubner WD. Pharmacopsychiatry 1997 Sep;30 Suppl 2:81-5

St. John’s ECG Better, Imipramine Worse: DB high dose (1800mg/d) hypericum vs imipramine 209 pt 6 weeks. ECG improved slightly with St. John’s but increase in 1st degree AV block and repolarization defects with imipramine. Germany. The effect of hypericum extract on cardiac conduction as seen in the electrocardiogram compared to that of imipramine. Czekalla J, Gastpar M, Hubner WD, Jager D. Pharmacopsychiatry 1997 Sep;30 Suppl 2:86-8

Venlafaxine Better than Imipramine on Life Functioning : Two DB PC studies by the manufacturers of Effexor with 459 depressed patients for "up to" 6 weeks report their medicaiton worked better on a general life functioning scale developed by NIMH. Can improvement in well-being and functioning be distinguished from depression improvement in antidepressant clinical trials? Pedersen RD, Pallay AG, Rudolph RL. Qual Life Res 2002 Feb;11(1):9-17

Venlafaxine Slightly Better than Imipramine Maintenance: DB 1 year study 290 pt on venlafaxine, 91 imipramine, both 75-225 mg/d. Trend in favor of venlafaxine. Eastside, New York City. Long-term safety and clinical acceptability of venlafaxine and imipramine in outpatients with major depression. Fewer side-effects said important in favor of venlafaxine. Shrivastava RK, Cohn C, Crowder J, Davidson J, Dunner D, Feighner J, Kiev A, Patrick R. J Clin Psychopharmacol 1994 Oct;14(5):322-9

Venlafaxine slightly Better than Imipramine at Penn: 244 pt DB PC 6 week aver max 182mg venlafaxine 176mg/d imipramine. 90% and 79% improved. Side-effect dropout 15% vs 24%. Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. Schweizer E, Feighner J, Mandos LA, Rickels K. J Clin Psychiatry 1994 Mar;55(3):104-8

Venlafaxine Faster Than Imipramine in Helping Depressed Melancholia: DB MDD melancholic inpatients rx venlafaxine 375/d vs imipramine 200/d. Response rate in both equal but time to average response 14 days venlafaxine vs. 21 days imipramine. More side-effects imipramine. A randomized, double-blind comparison of a rapidly escalating dose of venlafaxine and imipramine in inpatients with major depression and melancholia. U Mainz: Benkert O, Grunder G, Wetzel H, Hackett D. J Psychiatr Res 1996 Nov-Dec;30(6):441-51

Imipramine Alone Fine with Mood Congruent Psychosis: DB PC 52 pt, ¼ psychotic. Treated to a certain blood level. Psychotic patients 70% response and actually did better than non-psychotic. J Affect Disord 2001 Oct;66(2-3):165-74; Treatment of mood-congruent psychotic depression with imipramine. Bruijn JA, Moleman P, Mulder PG, van den Broek WW. Department of Psychiatry, University Hospital Rotterdam

300 mg Better: DB inpatient severely depressed neurotic and endogenous 51 pt MDD 300mg v 150/d. Side effects not clearly dose related. 1 numbness, 1 dizzy with incr BP, 2 agitation, 1 mania, 1 cramps & nausea, 2 rash. Neurotic and endogenous similar rates of improvement. Psychotic did less well but still had 50% response. Two dosages of imipramine in hospitalized endogenous and neurotic depressives. Simpson GM, Lee JH, Cuculic Z, Kellner R. Arch Gen Psychiatry 1976 Sep;33(9):1093-1102

Low-Dose 100mg/d Tricyclics Work: Low dosage was defined as 100mg/d or less of imipramine, amitriptyline, clomipramine, desipramine, doxepin, dothiepin, trimipramine, or lofepramine.  A meta-analysis found 35 trials comparing to placebo and sex to standard dose tricyclics.  Over 2000 and 551 patients involved.  No added benefit to standard dose tricyclics but higher side-effect with twice the dropouts as with low dose. Low dose 1.5 times more likely than placebo to lower depression 50%. Meta-analysis of effects and side-effects of low dosage tricyclic antidepressants in depression: systematic review. Toshi A. Furukawa, et al. BMJ 2002;325:991-5.

Blood Level 110-140 nanog/mL Best for Phobia & Panic: DB PC 80pt 8 week imipramine 0.5mg/kg/d or 1.5 or 3.0. Only 1.5 and 3.0 did better than placebo and they were equal. Phobias did best between 110-140 and panic best as approached 140 and no better if high. Dropouts due to side-effects 6%, 15%, and 36%. Ohio State. Imipramine treatment of panic disorder with agoraphobia: dose ranging and plasma level-response relationships. Mavissakalian MR, Perel JM. Am J Psychiatry 1995 May;152(5):673-82

Two Week Improvement Predicts Response: In two large trials comparing imipramine to brofaromine, an MAO-A Inhibitor. Predictive effect not as strong with elderly. Bonn. Effect of initial treatment with antidepressants as a predictor of outcome after 8 weeks. Volz HP, Muller H, Sturm Y, Preussler B, Moller HJ.

One Week Improvement Predicts Response to Fluvoxamine: DB PC imipramine vs fluvoxamine. 82.5% of responders already showed improvement by end of week 1. The efficacy of fluvoxamine in patients with severe depression. Ottevanger EA. Prog Neuropsychopharmacol Biol Psychiatry 1994 Jul;18(4):731-40

SAMe + Imipramine Faster than Imipramine in DB: 40 pt DB PC imipramine 150/d with or without SAMe 200mg IM x 2 weeks. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Mexico. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Psychiatry Res 1992 Dec;44 (3):257-62

Switching to or from Imipramine to or from Sertraline Works: 115 sertraline failures and 57 imipramine failures after 12 week trials were switched to the opposite medication. In both groups, the response rate was good although sertraline (60% intent to treat) did non-significantly better due to imipramine (44% intent to treat) side-effect dropouts (bethanechol not used). 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. Arch Gen Psychiatry 2002 Mar;59(3):233-9

Recommend 5 Year Maintenance if Two Episodes Less Than 2.5 years Apart: DB PC of patients doing well after 3 years of imipramine 200/d. Two more years of maintenance did better than placebo. U Pitt. Five-year outcome for maintenance therapies in recurrent depression. Kupfer DJ, Frank E, Perel JM, Cornes C, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ. Arch Gen Psychiatry 1992 Oct;49(10):769-73

Imipramine 3 Year Maintenance Very Helpful, Psychotherapy Modest Benefit: 128 pt recurrent depression DB PC after responding to imipramine and interpersonal psychotherapy. Therapy was Qmonth. Maintenance averaged 200mg/d. U Pitt. Three-year outcomes for maintenance therapies in recurrent depression. Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ. Arch Gen Psychiatry 1990 Dec;47(12):1093-9

Double-Blind Aren’t Blind: Large majority of patients knew whether they received an active medication in a study of alprazolam, imipramine, and placebo and the large majority of physicians accurately guessed which med the patients had been given. Germany. How "blind" are double-blind studies? Margraf J, Ehlers A, Roth WT, Clark DB, Sheikh J, Agras WS, Taylor CB. J Consult Clin Psychol 1991 Feb;59(1):184-7

Double-Blind Not Blind: 78% patients and 87% of physicians correctly guessed whether patient on active medicine or placebo in a 137 pt 6 week phenelzine-imipramine-placebo study. Outcome, side-effects, other unspecified cues seem to break the blind. How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine. Rabkin JG, Markowitz JS, Stewart J, McGrath P, Harrison W, Quitkin FM, Klein DF. Psychiatry Res 1986 Sep;19(1):75-86

Imipramine Rx Post-Psychotic Depression Reduces Psychotic Relapse: DB PC 24 schiz of fluphenazine decanoate & benztropine who had imipramine started for depression and responded. Placebo tappered off imipramine and showed greater relapse into psychosis. Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial. Siris SG, Bermanzohn PC, Mason SE, Shuwall MA. Arch Gen Psychiatry 1994 Feb;51(2):109-15

Imipramine Maintenance for Agoraphobia: 51 pt who had remitted on 2.25mg/kg/d of imipramine were DB PC after 6 months with half stopping immediately and the other stopped 6 month or later. The relapse rates were identical at 37% each. The abstract is unclear when the relapses occurred. Researchers were unable to find any predictors of relapse. Duration of imipramine therapy and relapse in panic disorder with agoraphobia. U Pitt & Case Western: Mavissakalian MR, Perel JM. J Clin Psychopharmacol 2002 Jun;22(3):294-9 Same study found dry mouth, sweating, and increased heart rate constitute a significant and specific enduring burden of imipramine maintenance treatment. The data also revealed that weight gain is a significant and specific side effect of 1-year imipramine maintenance treatment; however, the likelihood of reporting sexual dysfunction decreased over time, with no difference between the placebo and imipramine. Specific side effects of long-term imipramine management of panic disorder. Mavissakalian M, Perel J, Guo S. J Clin Psychopharmacol 2002 Apr;22(2):155-61

Imipramine Helps School Refusal is DB: CBT with or without imipramine in DB PC of 63 children with school refusal and co-morbid GAD or MDD for 8 weeks studied. Days in school for imipramine group 70%, for placebo group 27%. Imipramine plus cognitive-behavioral therapy in the treatment of school refusal. U Minn, Bernstein GA, Borchardt CM, Perwien AR, Crosby RD, Kushner MG, Thuras PD, Last CG. J Am Acad Child Adolesc Psychiatry 2000 Mar;39(3):276-83

Tricyclics Help Functional Nausea, Vomiting: Chart review open study of 37 pt with chronic nausea & vomiting and negative w/u, only 11 with anx or depr. 51% complete resolution, 84% at least moderate reduciton. tertiary amines (amitrip, imip, dox) better than secondary (nortrip, desip). All had failed other treatments. Digestive diseases & Sci 98;43:1951

Imipramine Helps Alopecia Areata: DB PC 14 pt 6 months. 5 of 7 imipramine but 0 of 7 placebo patients showed hair regrowth. Condition characterized by high anxiety and depression but both groups had decrease in psychic symptoms. Imipramine in alopecia areata. A double-blind, placebo-controlled study. Perini G, Zara M, Cipriani R, Carraro C, Preti A, Gava F, Coghi P, Peserico A. Psychother Psychosom 1994;61(3-4):195-8

Imipramine Helps Weight Loss: DB PC 8week study with 6 month open trial follow-up. Imipramine groups lost 4# in 8 weeks and 11# in all after 8 months vs. no change in placebo group. Imipramine and diet counseling with psychological support in the treatment of obese binge eaters: a randomized, placebo-controlled double-blind study. Laederach-Hofmann K, Graf C, Horber F, Lippuner K, Lederer S, Michel R, Schneider M. Int J Eat Disord 1999 Nov;26(3):231-44 U Berne

Imipramine Helps Reduce Drug Use in Depressed Abusers: DB PC 137 pt for 12 weeks methadone patients with primary DSM-IIIR depressive and greater than 4 weeks on stable methadone. Response defined as much improvement on CGI and 75% decrease drug use. 84 patients in analysis after at least 6 weeks in study. Imipramine had 57% response vs 7% placebo. Imipramine treatment of opiate-dependent patients with depressive disorders. A placebo-controlled trial. Nunes EV, Quitkin FM, Donovan SJ, Deliyannides D, Ocepek-Welikson K, Koenig T, Brady R, McGrath PJ, Woody G. Arch Gen Psychiatry 1998 Feb;55(2):153-60

Imipramine > Chloral Hydrate for Pediatric Acute burn Disorder Stress: 25 children DB PC 1 week. Average 45% burned. 83% vs 38% responders. Shriners, Galveston. Imipramine treatment in pediatric burn patients with symptoms of acute stress disorder: a pilot study. Robert R, Blakeney PE, Villarreal C, Rosenberg L, Meyer WJ 3rd. J Am Acad Child Adolesc Psychiatry 1999 Jul;38(7):873-82

No Increase Suicidal Ideation in TCA, Fluoxetine, Placebo: 17 BD PC 3065 pt comparing fluoxetine, TCA, and placebo. Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression. Tollefson GD, Rampey AH Jr, Beasley CM Jr, Enas GG, Potvin JH. J Clin Psychopharmacol 1994 Jun;14(3):163-9

Texas Recommends TCAs as First Line Rx for Psychotic Depression: While SSRIs recommended for non-psychotic, Texas says only TCAs systematically studied for psychotic. Psych Drug Alerts, 1999

TCA Blood Levels: If done, need only do once. Wait seven days till dose stable, draw 12 hr after last dose. Levels for imipramine, desipramine, amitriptyline, nortriptyline determined. Levels over 500mg (or microg?)/ml associated with tremors, agitation, confusion, and ataxia. Currents 10/88

TCA Blood Levels Not Related to Response: Study of patients on imipramine or amitriptyline at 250mg/d each. No relationship of any type between efficacy and plasma level. Imipramine and amitriptyline plasma concentrations and clinical response in major depression. Kocsis JH, Hanin I, Bowden C, Brunswick D. Br J Psychiatry 1986 Jan;148:52-7

Imipramine Helps Chest Pain with Normal Coronary Angiograms: Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. These patients may have a visceral pain syndrome unrelated to myocardial ischemia. Sixty patients with chest pain and normal coronary angiograms underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then were treated in a DB PC 3-week study of clonidine at 0.1 mg twice daily, imipramine 50 mg nightly or placebo. 22% had ischemic-appearing electrocardiographic responses to exercise, 41% had abnormal esophageal motility, 63% had one or more psychiatric disorders, and 87% had their characteristic chest pain provoked by right ventricular electrical stimulation or intracoronary infusion of adenosine. Imipramine caused a reduction of 52% in episodes of chest pain, clonidine 39%, and placebo 1%. Repeat assessment of sensitivity to cardiac pain while the patients were receiving treatment showed significant improvement only in the imipramine group (P = 0.01). The response to imipramine did not depend on the results of cardiac, esophageal, or psychiatric testing at base line, or on the change in the psychiatric profile during the course of the study, which generally improved in all three study groups. Imipramine in patients with chest pain despite normal coronary angiograms. Cannon RO 3rd, Quyyumi AA, et al. NIH. N Engl J Med. 1994 May 19;330(20):1411-7

TCA’s More Side-Effects vs SSRIs in DB:25 DB studies comparing the two families. TCA’s tended to be more effective, but it was the dual action TCA’s amitriptyline and clomipramine, while the noradrenergic TCA’s imipramine, despramine were not superior. More patients overall discontinued treatment on TCAs than on SSRIs (29.0% vs. 25.5%), although this did not reach statistical significance (RR = 0.88, P = 0.121). Significantly more patients stopped treatment due to adverse effects on TCAs compared to SSRIs (14.2% vs. 9.1%, RR = 0.66, 95% CI 0.50 to 0.87, P = 0.003) with no difference in discontinuations due to treatment failure (10% vs. 11.6%). SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Anderson IM. Depress Anxiety 1998;7 Suppl 1:11-7

TCA Put Down in Guidelines Due to Tolerability in DBs: (SSRIs) are the first-line treatment for panic disorder. Tricyclic antidepressants (TCAs) are equally effective, but they are less well tolerated than the SSRIs. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ; World Federation of Societies of Biological Psychiatry Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders. World J Biol Psychiatry 2002 Oct;3(4):171-99

Imipramine Weight Gain 3# in Two Years: 115 patients we monitored weight change during the three-year maintenance treatment phase to the point of trial completion, recurrence or termination. No differences were noted between individuals receiving active medication (average gain of 5.8 lbs. during an average treatment period of 725 days) versus those randomized to the 'no-drug' cells (average gain of 2.8 lbs. during an average treatment period of 422 days). Kupfer, U Pitt, J Affect Disord 1992 Sep;26(1):65-72

Less Weight Gain in Nursing Home on TCAs: Clinically important weight loss and gain occurred at 6 months in 14.8% and 14.4% of the sample, respectively. In unadjusted analyses, an increased likelihood of loss was found for users of SSRIs (Odds Ratio 1.57) and others (OR 1.89), compared with none. In logistic models accounting for potential confounding factors, however, SSRI use showed a modest association with gain (OR 1.31) and a trend toward a similarly modest association with loss (OR 1.28). TCA use was not associated with weight gain. When weight was examined as a continuous variable, all groups demonstrated a broad range of both loss and gain with mean-unadjusted weight changes < 3 pounds. Rigler, U Kansas, J Am Geriatr Soc 2001 Jan;49(1):49-55

Hip Fractures No Different on SSRI vs Tricyclic Antidepressants: Anti-depressants increase hip fractures with an RR 2.4 but there is no advantage of SSRI over TCA although lower dosage of either is better. Tertiary amine TCAs did do a little better than secondary amines which were same as SSRIs. Lancet ’98;351:1303-7

MP Rash Not Require D/C: Study of 205 children on desipramine found 12 got maculo-papular rash lasting 2-7 days without other difficulties. Only 1 of 8 continuing meds developed another rash, which subsided without incident. For MP Rash, imipramine can be continued with careful evaluation and medical f/u. J Biederman, MGH, J Clin Psyc 88;49:178-83

Sexual Dysfunction with Imipramine, Phenelzine Common: In 6 week DB PC sexual side-effects were common, especially in men, orgasm and ejaculation more than erection. Effects of antidepressant medication on sexual function: a controlled study. Harrison WM, Rabkin JG, Ehrhardt AA, Stewart JW, McGrath PJ, Ross D, Quitkin FM. J Clin Psychopharmacol 1986 Jun;6(3):144-9

Imipramine Raised Blood Sugar; Fluoxetine (Prozac) Lower It: In a 60 healthy Major Depression patient, 8-week DB PC study, patients on fluoxetine 20-40 mg/day had a decrease in fasting blood sugar (FBS) from 88 to 80 while those on imipramine had an increase from 87 to 97. Ghaeli P, Shahsavand E, Mesbahi M, Kamkar MZ, Sadeghi M, Dashti-Khavidaki S. Tehran University. J Clin Psychopharmacol. 2004 Aug;24(4):386-8