Other Warnings/Precautions

• Use of thyroid hormones in the therapy of obesity, alone or in combination, is not effective at doses within the range of daily hormonal requirements; larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines

• Use of thyroid hormones is not justified for the treatment of male or female infertility unless accompanied by hypothyroidism

• Use with caution in patients in whom the integrity of the cardiovascular system is suspected, including elderly patients or those with angina pectoris

• Thyroid hormone therapy in patients with concomitant diabetes mellitus or insipidus or adrenal cortical insufficiency aggravates the intensity of their symptoms

Do Not Use

• If patient has uncorrected adrenal cortical insufficiency

• If patient has untreated thyrotoxicosis

• If there is a proven allergy to triiodothyronine

TRIIODOTHYRONINE: SPECIAL POPULATIONS

Renal Impairment

• No dose adjustment necessary

Hepatic Impairment

• No dose adjustment necessary

Cardiac Impairment

• Use with caution

• Requires dose reduction: initial 5 mcg; increase by no more than 5 mcg at 2-week intervals; reduce dose if cardiovascular disease is aggravated

Elderly

• Some patients may tolerate lower doses better

Children and Adolescents

• Thyroid hormone is used safely in infants, children, and adolescents for hypothyroidism

• Not studied for use as adjunct in depression

Pregnancy

• Risk Category A [adequate, well-controlled studies in pregnant women have failed to demonstrate risk to the fetus]

• Thyroid hormones do not readily cross the placental barrier, and the clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones are administered to pregnant women

Breast Feeding

• Some drug is found in mother’s breast milk

• No known adverse effects but use should be cautious

• Must weigh benefits of breast feeding with risks and benefits of treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding

TRIIODOTHYRONINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with lethargy and fatigue

• Patients with unstable or rapidly fluctuating mood

Potential Disadvantages

• Patients with osteoporosis

• Patients already taking thyroid replacement

Primary Target Symptoms

• Depressed mood

Pearls

• Have periodic monitoring by primary care physician, including neck examination and thyroid palpation

• Generally well tolerated, especially compared to other augmentation options for depression

• May be useful in stabilizing fluctuating mood states as well as improving depressed mood

Suggested Reading

Aronson R, Offman HJ, Joffe RT, et al. Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry 1996;53:842–8.

Connolly KR, Thase ME. If at first you don’t succeed: a review of the evidence for antidepressant augmentation, combination and switching strategies. Drugs 2011;71(1):43–64.

Garlow SJ, Dunlop BW, Ninan PT, Nemeroff CB. The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder. J Psychiatr Res 2012;46(11):1406–13.

Hage MP, Azar ST. The link between thyroid function and depression. J Thyroid Res 2012;2012:590648.

Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 2006;163:1519–30.

TRIMIPRAMINE

TRIMIPRAMINE: THERAPEUTICS

Brands

• Surmontil

see index for additional brand names

Generic?

Yes

Class

• Tricyclic antidepressant (TCA)

• Serotonin and norepinephrine/noradrenaline reuptake inhibitor

Commonly Prescribed for

(bold for FDA approved)

• Depression

• Endogenous depression

• Anxiety

• Insomnia

• Neuropathic pain/chronic pain

• Treatment-resistant depression

How the Drug Works

• Boosts neurotransmitters serotonin and norepinephrine/noradrenaline

• Blocks serotonin reuptake pump (serotonin transporter), presumably increasing serotonergic neurotransmission

• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission

• Presumably desensitizes both serotonin 1A receptors and beta adrenergic receptors

• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, trimipramine can increase dopamine neurotransmission in this part of the brain