Tricyclic Antidepressants

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References

Awad AG. Diet and drug interactions in the treatment of mental illness--a review. Can J Psychiatry 1984 Nov;29(7):609-613 (Review)

Bagheri H, Schmitt L, Berlan M, Montastruc JL. Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy volunteers and in depressed patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1992 Dec;34(6):555-558.
Abstract: The effect of yohimbine treatment (4 mg three times daily) for 3 weeks on salivary secretion was investigated. In healthy volunteers, acute administration of yohimbine increased salivary volume within 1 h to a similar extent before and at the end of the treatment period. In depressed patients treated with tricyclic antidepressants (and exhibiting a reduced salivary flow), yohimbine also acutely increased salivary volume. In contrast, the alpha 2-adrenoceptor antagonist failed to modify resting values measured in the morning (i.e. 10 and 14 h after the last administration in healthy volunteers and depressed patients respectively). This result indicates that alpha 2-adrenoceptor antagonists may have a potential therapeutic use in the treatment of dry mouth caused by tricyclic antidepressant drugs.

Bagheri H, Picault P, Schmitt L, Houin G, Berlan M, Montastruc JL. Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary secretion in patients treated with tricyclic antidepressants. Br J Clin Pharmacol 1994 Jan;37(1):93-96.
Abstract: The pharmacokinetic parameters and the time course of the effect after acute oral administration of yohimbine on salivary secretion in patients treated with tricyclic antidepressants were investigated. Yohimbine (10 mg) increased both salivary outflow and plasma noradrenaline levels for 4 h. Pharmacokinetic parameters (t1/2, tmax, Cmax and AUCexp) and plasma concentrations of noradrenaline were higher in patients treated with tricyclic antidepressants than in controls. At this dose, yohimbine induced a relatively large number of side effects. A lower dose (4 mg) increased salivary secretion for 3 h without any side effects in patients treated with tricyclic antidepressants but not in healthy volunteers. These data describe an interaction between yohimbine and tricyclic antidepressants and thus show that a relatively low dose (4 mg) of yohimbine could be useful in the treatment of dry mouth due to tricyclic antidepressants.

Beckstrom D, Reding R, Cerletty J. Syndrome of inappropriate antidiuretic hormone secretion associated with amitriptyline administration. JAMA 1979 Jan 12;241(2):133. (Letter)

Berken GH, Weinstein DO, Stern WC. Weight gain. A side-effect of tricyclic antidepressants. J Affect Disord 1984 Oct;7(2):133-138.
Abstract: Body weight and appetite were evaluated in 40 depressed outpatients from a private psychiatric practice who were receiving low-modest doses of tricyclic antidepressants. Amitriptyline (maximum of 150 mg/day), nortriptyline (maximum of 50 mg/day), and imipramine (maximum of 80 mg/day) were given for an average of 6 months of treatment. There was a mean weight increase of 1.3-2.9 lbs/month, which led to an average total weight gain of 3-16 lbs, depending on drug, dose and duration. These weight increases were linear over time and were accompanied by marked increases in the preference for sweets. Ultimately, excessive weight gain was the most common cause of discontinuation of treatment, occurring in one-half of the patients. Significant weight loss occurred upon discontinuation of drug. These findings show that chronic administration of low-modest doses of tricyclic antidepressants frequently cause considerable weight gain and can significantly interfere with the ability to provide long-term maintenance therapy.

Fernstrom MH. Depression, antidepressants, and body weight change. Ann N Y Acad Sci 1989;575:31-39; discussion 39-40. (Review)
Abstract: The excessive weight gain observed during treatment of depression with antidepressant medications is caused in part, at least in some persons, by reductions in resting metabolic rate. Such problematic weight gain appears unrelated to clinical recovery, weight change during the depressive episode, prior weight, or other related factors. Preliminary results suggest that increased energy efficiency (of about 16-24%) during treatment with tricyclic antidepressants could promote weight gain even in the absence of a change in caloric intake. This is not a property of all antidepressants, as demonstrated by the increase in metabolic rate and associated weight loss observed during treatment with the monocyclic antidepressant compound fluvoxamine. Should these serotonergic compounds continue to be effective antidepressants, they may be better accepted by patients, and their use help avoid medication noncompliance. In considering energy balance and weight change, our focus has been drawn to altered metabolic rate. Continuing studies do not suggest an effect of antidepressants on appetite, particularly the presence of "carbohydrate craving," either during treatment or during a depressive episode. Certainly, a notable preference for highly palatable foods (rich in fats and carbohydrates) occurs during the depressive episode, but not during treatment. These foods cannot be labeled carbohydrates.

Fernstrom MH. Drugs that cause weight gain. Obes Res 1995 Nov;3 Suppl 4:435S-439S. (Review)
Abstract: Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent and problematic body weight gain in many treated patients. Major depressive illness is often associated with reductions in appetite and body weight, and treatment with antidepressants effectively restores mood, appetite and weight. However, a frequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, often times resulting in medication noncompliance. The incidence of weight gain during acute and chronic treatment with different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain.

Glassman AH, Roose SP. Risks of antidepressants in the elderly: tricyclic antidepressants and arrhythmia-revising risks. Gerontology 1994;40 Suppl 1:15-20.
Abstract: Unexpected events have occurred in cardiology over the last 4 years. A study by the Heart and Lung Institute of the National Institute of Health in the mid-1980s showed to great surprise that class I antiarrhythmic drugs given to patients with ventricular arrhythmias following myocardial infarction, instead of preventing deaths, actually increased the number of patients dying. Since then, a series of studies has consistently confirmed this original observation. The problem for psychiatry is that the tricyclic antidepressant (TCA) drugs are also class I antiarrhythmics. There is every reason to believe that a similar increased risk of death would exist with the TCAs. It is, therefore, important for psychiatrists to understand the cause and magnitude of this excess in deaths. Evidence to date would suggest that all class I compounds, despite being powerful antiarrhythmics under usual physiological conditions, become proarrhythmic under anoxic conditions. Such conditions would exist in ischaemic heart disease during angina and, particularly, myocardial infarction. How this might alter our use of TCAs and whether this happens with the selective serotonin reuptake inhibitors is discussed.

Folkers K. Basic chemical research on coenzyme Q10 and integrated clinical research on therapy of diseases. In G Lenaz, ed. Coenzyme Q. John Wiley and Sons, 1985.

Goodman and Gilman A, eds. The Pharmacological Basis of Therapeutics. 6th Edition. New York: MacMillan Co., 1980: 1331-1346, 1551-1601.

Gram LF. Dose-effect relationships for tricyclic antidepressants: the basis for rational clinical testing of new antidepressants. Psychopharmacol Ser. 1993;10:163-173. (Review)

Kerr JS, Powell J, Hindmarch I. The effects of reboxetine and amitriptyline, with and without alcohol on cognitive function and psychomotor performance. Br J Clin Pharmacol 1996 Aug;42(2):239-241.

Kishi T, Makino K, Okamoto T, et al. In Yamamura Y, Folkers K, Ito Y, eds. Biochemical and Clinical Aspects of Coenzyme Q, Volume II. Amsterdam: Elsevier/North Holland Biomedical Press, 1980: 139-157.

Lasswell WL Jr, Weber SS, Wilkins JM. In vitro interaction of neuroleptics and tricyclic antidepressants with coffee, tea, and gallotannic acid. J Pharm Sci 1984 Aug;73(8):1056-1058.
Abstract: The in vitro interaction of selected drugs with coffee, tea, gallic acid, and gallotannic acid was examined by mixing solutions of drug with each of these four preparations. Results of these experiments indicate that significant precipitation occurs for a variety of agents, including several phenothiazines, amitriptyline, haloperidol, imipramine, and loxapine. The strong complex which is formed between these drugs and tannins is probably the basis of the interaction of these drugs with coffee and tea. Although precipitates did occur with a number of neuroleptics, two members of this drug class, thiothixene and molindone, failed to interact with the solutions used.

Luzecky MH, Burman KD, Schultz ER. The syndrome of inappropriate secretion of antidiuretic hormone associated with amitriptyline administration. South Med J 1974 Apr;67(4):495-497.

Pinto J, Huang YP, Pelliccione N, Rivlin RS. Cardiac sensitivity to the inhibitory effects of chlorpromazine, imipramine and amitriptyline upon formation of flavins. Biochem Pharmacol 1982 Nov 1;31(21):3495-3499.
Abstract: Chlorpromazine, imipramine and amitriptyline, drugs structurally related to riboflavin, each inhibited the formation in vivo of flavin adenine dinucleotide (FAD) from riboflavin in rat heart at 2-5 mg/kg body weight, doses comparable on a weight basis to those used clinically. All three drugs inhibited FAD formation in heart within 5 hr after a single dose of 25 mg/kg. Chlorpromazine under these conditions also inhibited FAD formation in liver, cerebrum and cerebellum. A series of psychoactive agents structurally unrelated to riboflavin did not inhibit flavin formation in the organs tested. These findings indicate that the inhibitory effects of the drugs studied have organ specificity with respect to FAD formation.

Pinto J, Huang YP, Rivlin RS. Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline. J Clin Invest. 1981 May;67(5):1500-1506.

Rispail Y, Schmitt L, Berlan M, Montastruc JL, Montastruc P. Yohimbine increases salivary secretion in depressed patients treated with tricyclic antidepressants. Eur J Clin Pharmacol 1990;39(4):425-426.

Scahill L, Lynch KA. Tricyclic antidepressants: cardiac effects and clinical implications. J Child Adolesc Psychiatr Nurs 1994 Jan-Mar;7(1):37-39.

Solammadevi SV. Inappropriate antidiuresis during amitriptyline therapy. South Med J 1981 Jun;74(6):775-776. (Letter)

Stein EM, Stein S, Linn MW. Geriatric sweet tooth. A problem with tricyclics. J Am Geriatr Soc 1985 Oct;33(10):687-962.
Abstract: Ninety-three consecutive outpatients receiving tricyclic antidepressants for at least one month were asked about medication side effects, including excessive appetite and craving for sweets. Prevalence of these side effects and their relationship (Pearson r) to type of medication, dosage, patient characteristics, diagnoses, weight gain, and clinical improvement were examined. More than one-third (38%) reported excessive appetite, 34% had a craving for sweets, and about one-half (48%) had either one or the other of these reactions. These adverse side effects were related significantly to weight gain (P less than .001) and a higher dose of medication, but not to clinical improvement. Clinical improvement was in the moderate-to-good range but was not related to medication dose. Because increasing degrees of overweight can pose serious health risks, especially for the elderly, it is critical for future research to examine ways of maintaining therapeutic benefit while minimizing food craving side effects. Methods of dealing with these issues clinically are suggested.

Threlkeld DS, ed. Central Nervous System Drugs, Antidepressants, Tricyclic Compounds. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1990.