Tricyclic antidepressants treatment-resistant depression

Tricyclic/tetracyclic antidepressants continue to be useful for severe or treatment-resistant depression... 

Mirtazapine is another antidepressant with a unique mechanism of action, enhancing serotonin and norepinephrine in a manner quite complex and distinct from venlafaxine or tricyclics. Like venlafaxine, it may be effective for severe or treatment-resistant depression, though its widespread use has been hampered by a high incidence... 

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

Amsterdam JD Use of high dose tranylcypromine in resistant depression, in Refractory Depression. Edited by Amsterdam JD. NewYork, Raven, 1991,pp 123-130 Amsterdam JD, Berwish N Treatment of refractory depression with combination re-serpine and tricyclic antidepressant therapy. J Clin Psychopharmacol 7 238-242, 1987... 

Post and Kramlinger (386) have also suggested that lithium added to carbamazepine may be useful in treatment-resistant mood-disordered patients. One possible basis for this approach is that carbamazepine, which has a tricyclic ring structure similar to imipramine, may sensitize postsynaptic serotonin receptors in a similar way to standard drugs such as imipramine. A mood stabilizer (e.g., lithium, valproate, carbamazepine) plus antidepressant may benefit some rapid cycling or mixed bipolar patients, attenuating the propensity to switch from mania to depression. 

Lithium augmentation of antidepressants is a well-established treatment for resistant depression and is usually well tolerated with all classes of antidepressants, although there have been a few reports of the serotonin syndrome with SSRIs (474). It is possible that shared adverse effects could be magnified by combining lithium with various antidepressants (for example tremor, weight gain, gastrointestinal upset). Hyponatremia secondary to the SIADH has been linked to SSRIs and tricyclic antidepressants, especially in elderly patients, and could predispose to lithium toxicity. 

The speed and efficacy of imipreunine in the treatment of depression were enhanced by the addition of thyroid hormone. 26 This combination was effective in patients who became resistant to the tricyclic antidepressives.27 increasing... 

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