Tricyclics were the original group of standard anti-depressant medications.  There are hundreds of studies with these medicines showing that they work as well or better than the popular SSRI medications and that patients on tricyclics kill themselves no more often than patients on SSRIs.  Drug company psychiatrists have attacked tricyclics for years as having more side-effects, especially anti-cholinergic side-effects.  

In fact, the most common anti-cholinergic side-effects are very easy to treat with bethanechol, but the drug company psychiatrists have not allowed bethanechol to be given to tricyclic patients in their studies.  Many of these drug company psychiatrists work at major universities and are regular speakers at national and international psychiatric conventions.  Why they have stacked the deck against tricyclics, no one knows. Unfortunately, thanks to poor regulation by the federal government, the cost of bethanechol has increased from $4 to $150 for a bottle of 100 25mg. pills in the last 12 years.  It is available from England for $25.  Bethanechol is great for any patient getting a dry mouth from their psychiatric medication.

Nortriptyline ($9-12/mo.) and clomipramine ($18-24/mo.) look particularly attractive as initial medications.  They are as effective as venlafaxine ($53-106/mo.) or any other available anti-depressant, but significantly less expensive.  They have safety indexes as good or better than venlafaxine.  And with the bethanechol available for patients who need it, they have no more and possibly even fewer side-effects than venlafaxine.  

Tricyclics As Good As SSRIs: A meta-analysis of DB studies comparing tricylics anti-depressants to the newer SSRIs reports no difference in efficacy except that the TCAs may be better for hospitalized and severely depressed, possibly due to the inhibition of norepinephrine reuptake as well as serotonin. I Anderson, J Psychopharm (Oxf) 8:238-49 ’94. Norpramin is an effective TCA anti-depressant with a primary effect on norepinephrine. ECT also increases the release of NE. Combination studies of fluoxetine and desipramin have found enhanced benefit.

Author Says Avoid Tricyclics in Cardiac Patients: Tricyclic antidepressants had been considered acceptable for use in patients with ischemic heart disease until data from the Cardiac Arrhythmia Suppression Trial (CAST) demonstrated a significantly increased mortality rate after myocardial infarction in patients treated with type I antiarrhythmics. Because tricyclic antidepressants are type IA antiarrhythmics, they presumably carry a risk similar to that of moricizine in patients with ischemic disease. The limited but growing data available on the use of selective serotonin reuptake inhibitors and bupropion in patients with cardiac disorders suggest that these agents are safer antidepressant treatment alternatives. Columbia U., Considerations for the use of antidepressants in patients with cardiovascular disease. Roose SP. Am Heart J 2000 Oct;140(4 Suppl):84-8. Ed: Animal research has demonstrated that tricyclics differ from other type 1 antiarrhythmics.  Extensive cardiac mortality research has shown that both tricyclics and SSRIs tend to decrease cardiac mortality and that there is no significant difference between the two families. See Tricyclic Mortality.

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

Transcranial Prefrontal Magnetic Stimulation More Effective on Right: In depression TPMS more effective on left. 16 patient DB study for mania with 10 days of 20 2 second trains per day. Grisaru, Ben Gurion U, Am J Psychiatry 11/98;155:1608

HS Dose Fewer Side-Effects: Single HS dose 60% fewer s-e. Done in DB study with the HS group taking all at bedtime right from the start. Improved med taking and non-significantly less depressed. Hussain, AJP 10/73. DB study of 75 found better recovery from depression with QD v BID. Elie, Montreal, Curr Ther Res 5/77

Seven Times Higher Death if OD: Retrospective study US OD data of Poison Control Centers. Desipramine the worst with 15 times newer anti-depressants. Chen, Columbia U, APA 5/30/98 Toronto.

Benztropine for TCA Withdrawal: Some withdrawal reactions due to cholinergic rebound hyperactivity. Restarting med or benztropine may help TCA withdrawal. Both tricyclic antidepressants and selective serotonin reuptake inhibitors cause similar syndromes, most commonly characterized by gastrointestinal or somatic distress, sleep disturbances, mood fluctuations and movement disorders. Case of akathisia from venlafaxine withdrawal. U Illinois. Antidepressant withdrawal reactions. Wolfe RM. Am Fam Physician 1997 Aug;56(2):455-62

Tricyclics Helps Suicidal Ideation, Alprazolam Doesn’t Worsen: Review by UpJohn of 22 DB studies of 3217 pt. Alprazolam did help suicidal ideation more than placebo and no increase in new ideation. risk of worsening of suicidal ideation was significantly less for the active-comparator group (the majority of patients in this group received amitriptyline or imipramine) than for alprazolam, and improvement of suicidal ideation occurred significantly more frequently in that group than in the alprazolam group. Alprazolam and suicidal ideation: a meta-analysis of controlled trials in the treatment of depression. Jonas JM, Hearron AE Jr., J Clin Psychopharmacol 1996 Jun;16(3):208-11

Amitriptyline > Fluoxetine in Parkinson’s Depressed: 77 DB Fluox 20-40/d vs amitrip 25-75/d. Average amitrip 35mg/d. More side-effectswith amitriptyline, but it was considerably more effective over 1 year of treatment. Equador. A comparison between low doses of amitriptyline and low doses of fluoxetin used in the control of depression in patients suffering from Parkinson's disease. Serrano Due as M, Rev Neurol 2002 Dec 1-15;35(11):1010-4

Low-Dose 100mg/d Tricyclics Work: Low dosage was defined as 100 mg/day or less of imipramine, amitriptyline, clomipramine, desipramine, doxepin, dothiepin, or trimipramine. A meta-analysis found 35 trials comparing to placebo and six to standard dose tricyclics with over 2551 patients involved found no added benefit to standard dose tricyclics but higher side-effect. Low dose was 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, BMJ 2002;325:991 

Tricyclics Might Help Functional Nausea, Vomiting: Chart review open study of 37 pt with chronic nausea & vomiting and negative w/u, only 11 with anxiety or depression. 51% complete resolution, 84% at least moderate reduction. Tertiary amines (amitriptyline, imipramine, doxepin) seemed better than secondary (nortriptyline, desipramine). All had failed other treatments. Digestive diseases & Sci 98;43:1951

TCA Blood Levels: If done, need only do only. 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

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