uestion:
Reconsider ECT as an option.uestion:
Reconsider ECT as an option.
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If you used an SSRI for the current, unsatisfactory medication trial, you could try a switch to venlafaxine. This would offer the possibility of combined serotonin and norepinephrine uptake inhibition and efficacy superior to an SSRI alone, without introducing the problematic cardiac side effect profile of a tricyclic. Some might prefer augmentation with lithium here, although SSRI augmentation with lithium is less robust than tricyclic augmentation with lithium.
T4 or stimulant augmentation might have adverse cardiac effects in this patient and hence would not be our first choice.
If bupropion is being used for the current, unsatisfactory antidepressant trial, augmentation with lithium may make some sense theoretically, although experience is limited. SSRI augmentation is also a plausible choice, since it would also add serotonergic input to bupropion's (probable) beta-adrenergic effect.¹ A second choice would be a switch to venlafaxine, as above.
The newest option that might apply in this situation (SSRI or bupropion failure) is mirtazapine (Remeron).² Click on the link for additional information. Mirtazapine is related to the antidepressant mianserin (frequently prescribed in England but not available here) and, like some tricyclics and venlafaxine, it enhances both noradrenergic and sertonergic neurotransmission. Efficacy appears comparable to amitriptyline (though the AMI doses were low), with some significant advantages in side effects: a benign cardiac profile³ including less orthostasis, apparent safety (including no EKG changes) in the limited number of overdoses recorded, low anticholinergic effects, and very low seizure rate (0.035%). On the other hand, there were significant problems with weight gain, somnolence, and dizziness. Agranulocytosis occurred in 2 of 2,796 patients, which prompted the Food and Drug Administration to require clinicians to warn patients of this possibility (see package insert), although no blood monitoring program is required as is the case with clozapine. The manufacturer reports that in the Netherlands, there were no cases of neutopenia in 13,500 mirtazapine-treated patients in post-marketing surveillance.* Furthermore, in the US, the manufacturer reports that as of May 1997 there were 125,000 prescriptions written, and the only case of agranulocytosis involved an AIDS patient who was on multiple medications.**
Recommendation #17
¹Bodkin JA et al. Combining SSRI's and bupropion in partial responders to antidepressant monotherapy. J Clin Psychiatry 1994;58:137-145.
²Hopkins HS. Mirtazapine. Biol Therapies in Psychiatry 1997;20(1):2-4
³Tulen JHM et al. Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine. J Clin Psychopharmacol 1996;16:135-145.
*Burrows GD, Kremer CME. Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol 1997;17[suppl 1]:34S-39S.
**Stahl SM, Sussman N. Mirtazapine: a clinical profile. Primary Psychiatry 1997;4(6):83.
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The following is provided to supplement the information given in the algorithm text regarding the use of this antidepressant. Please consult the package insert for full prescribing details before use.
Mirtazapine comes in 15 and 30 mg tablets, and has the advantage of once-a-day dosing. Due to its very sedating properties, it is usually given at bedtime, starting with 15 mg. This is increased to 30 mg after 1-2 weeks if the patient is not starting to improve (as tolerated).¹
Other advantages not noted before include an apparent lack of effect on cytochrome P450 enzymes IID6, IA2, and IIIA4 in vitro (though in vivo experience will be needed to determine the true rate of drug interactions), a lack of reported sexual side effects, and minimal headache, insomnia, and gastrointestinal side effects (all frequently a problem with the SSRI's or nefazodone). Anticholinergic effects seemed mild (dry mouth 10%, constipation 6%)²
Given the questions about agranulocytosis (mianserin also occasionally causes this), and the appetite stimulation and weight increase problems, it appears that use of mirtazapine will probably occur in second-line, treatment-resistant situations for the near future.³
¹Kehoe WA, Schorr RB. Focus on mirtazapine. Formulary 1996;31:455-469.
²Montgomery SA. Safety of mirtazapine: a review. Int Clin Psychopharmacol 1995;10 Suppl. 4:37-45.
³Kasper S. Efficacy of antidepressants in the treatment of severe depression: the place of mirtazapine. J Clin Psychopharmacol 1997;17[suppl 1]:19S-28S.