Rare Combinations of Ssris in Cotherapy with Other Antidepressants: The Importance of TDM

An adequate treatment of depressive disorders often necessitates a combination of several antidepressants. For the prevention of undesirable side-effects or drug interactions, therapeutic drug monitoring (TDM) is a safe and efficient procedure. We document 4 cases of combinations of fluoxetine with clomipramine or moclobemide and escitalopram.

In case 1, the therapeutic aim was to augment and stabilise the patient's clomipramine plasma levels and also to reduce the dose of the CYP2D6 substrate clomipramine by the addition of fluoxetine, a potent CYP 2D6 inhibitor. Notably, a relatively small dose of fluoxetine (20mg/d) was effective in raising the plasma level of norclomipramine, the metabolite to a (theoretically) subtoxic degree. Clinically, the increasing remission was documented by a decrease of scores in the Hamilton Depression Scale (HAM-D) from 32 to 18, with no apparent untoward drug effects.

Regarding patient 2, the combination of 20mg/d fluoxetine with 900mg/d moclobemide neither led to a „serotonergic syndrome“ nor to an increase of the RIMA plasma levels. Except for mild hypotension (100/60mmHg), no medication-related adverse effect could be observed.

Case reports 3 and 4 describe successful treatment combining escitalopram and fluoxetine. Addition of fluoxetine to an ongoing escitalopram treatment did not result in untoward effects but to an increase of escitalopram levels. In summary, TDM has proved to be a valuable tool in psychiatric clinical practice for optimization of psychopharmacological treatment. Using this technique in well-selected cases and with clear indication, also rare combinations of antidepressants may ensure clinical success in otherwise treatment-refractory patients.