Letters to the Editor
Combined Oral Venlafaxine and Intravenous Clomipramine-A: Successful Temporary Response in a Patient With Extremely Refractory Depression
Dear Editor:
We report a case of a married woman, aged 33 years, with treatment-refractory dependent and borderline personality disorder and major depression with atypical features, diagnosed according to DSM-IV criteria. She began to experience free-floating anxiety and incomplete panic attacks at age 26 years, which were soon followed by major depression. Two years later, at age 28 years, she presented to our outpatient clinic. She had already attempted suicide once by swallowing pills a couple of months prior to presenting. Her psychiatric family history was blank.
Given 1 mg dexamethasone, she was a nonsuppressor on the dexamethasone suppression test (DST) (based on the cut-off point of 5 µg/dL plasma cortisol) and had blunted response to 30 mg dexfenfluramine challenge test (cut-off 50 µU/L prolactin). Brain-imaging single photon emission computed tomography (SPECT) showed increased regional cerebral blood flow in the frontal lobes (+1.5 sd) and reduced regional cerebral blood flow (–0.3 to –1.4 sd) in the rest of brain areas.
The patient received the following adequate but unsuccessful treatment trials (including combinations) lasting at least 4 months each: 60 mg fluoxetine, 375 mg venlafaxine, 40 mg haloperidol, 6 mg risperidone, lithium (plasma levels 1.0 mEq/L), carbamazepine (plasma levels 9 µg/mL). She also had 8 clomipramine infusions (maximum 4 ampoules), with partial and unstable response for a couple of days. She refused ECT. During the last year, she has had rare mood-congruent auditory hallucinations.
We decided to try a more aggressive treatment with high dosages of intravenous (IV) clomipramine plus oral venlafaxine. The maximum dosage reached at day 15 was 6 ampoules IV clomipramine plus 225 mg oral venlafaxine.
On day 15, the patient responded with a dramatic remission of symptoms, almost to normothymic state. Her overall Hamilton Depression Rating Scale (HDRS) score decreased from 37 to 11, and her Hamilton Anxiety Rating Scale score decreased from 46 to 22. On the following HDRS indexes, her scores were as follows: depression symptoms decreased from 18 to 2; anxiety symptoms decreased from 8 to 6; insomnia symptoms decreased from 6 to 3; and nonspecific symptoms decreased from 5 to 0. This remission lasted for 37 days; then, obeying auditory hallucinations, the patient unsuccessfully attempted suicide by swallowing 30 tablets of diazepam 10 mg and thioridazine 30 mg. The mood change was acute, occurring within a few hours.
Clomipramine is not approved by the FDA for the treatment of depression; in continental Europe, however, it is considered the most effective agent, although there are only 5 published studies on its use to treat refractory depression (1–5). Our report is the first one on the combined use of oral venlafaxine and clomipramine infusions. The only prior combined treatment reported concerns maprotiline.
The usual practice of infusions suggests starting with one-half ampoule of clomipramine and adding 1 ampoule every day to reach a maximum of 5 to 6 ampoules. Anecdotal data report higher dosages of 8 to 9 ampoules daily.
References
1. Sallee F, Vrindavanam N, Deas-Nesmith D, Carson S, Sethuraman G. Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial. Am J Psychiatry 1997;154:668–73.
2. Bogdanowicz E, Kalinowski A, Swiecicki L. Treatment of depression with intravenous infusions of clomipramine and maprotiline. Psychiatr Pol 1991;25(3–4):19–24.
3. Zapletalek M, Zbytovsky J, Kudrnova K. Clinical experience with maprotilin and maprotilin/clomipramine infusions in resistant depression. Activitas Nervosa Superior (Praha) 1982;24(2):73–6.
4. Laux G, Reimer F. Treatment of therapy resistant depressions with high dose clomipramine. Int Pharmacopsychiatry 1979;14:29–9.
5. Ravizza L. Clinical and biochemical contributions on the effect of maprotiline and clomipramine in depressive states. Psychiatria Clinica (Basel) 1979;12:164–72.
Kostas N Fountoulakis, MD, PhD
Apostolos Iacovides, MD, PhD
George St Kaprinis, MD, PhD
Thessaloniki, Greece
|
