The utility of intravenous clomipramine in a case of Cotard's syndrome

Dear Editor,

We present a case of Cotard's syndrome in a 50-year-old female patient with no known prior history of medical or psychiatric illness. The patient went to the emergency department accompanied by a family member. She had been experiencing progressive depressive symptoms for 2 months. The patient presented with sadness, anhedonia, fatigue, insomnia, apathy, feelings of self-depreciation, and emotional instability, which was not related to any life-events. In the previous week, she started to feel hopelessness and anger; she also believed that her body was putrid. The mental state examination revealed depressive mood associated with psychomotor retardation, ruminative thoughts of death, delusional ideas of ruin, nihilistic delusions concerning her own body, and absence of insight. Physical and neurological examination, basic blood investigations, cerebral computed tomography, illicit drug screening, and electroencephalography showed no relevant alterations. There was no personal history of substance misuse.

She was admitted to the psychiatric department. Initial treatment consisted of paroxetine 20 mg/day and olanzapine 15 mg/day. After 4 days, there was no therapeutic response and her depressive symptoms were aggravated, showing mutism and poor collaboration. Because the standard oral antidepressant failed and the patient refused to feed and take oral medication, glucose-saline solution and intravenous clomipramine were started. Clomipramine is one of the few antidepressants that are available for parenteral administration. Increments of 25 mg of clomipramine were added daily reaching the maximum dose of 100 mg/day after 4 days. At this time, the patient showed improvement in her clinical status and began to feed normally. We started oral clomipramine, which was raised to 150 mg/day with increments of 25 mg/day in two divided doses, and discontinued intravenous clomipramine (also 25 mg/day); the patient also restarted taking olanzapine 10 mg/day.

After 10 more days of hospital stay, there was a progressive and substantial improvement of the clinical status; the depressive symptoms, delusional ideas of ruin, and nihilistic delusions concerning her own body were in remission. The patient was discharged and referred to psychiatric outpatient treatment maintaining oral clomipramine 150 mg/day and olanzapine 10 mg/day.

In our clinical experience, we found that intravenous clomipramine can be useful to treat resistant-depression and obsessive compulsive disorder when standard oral antidepressant treatment fails.¹ The limited available literature also suggests that it can promote an apparent faster clinical improvement compared with oral antidepressants. ^2-6 The low demethylation that results from the avoidance of the first-pass effect on hepatic metabolism led to a higher ratio of serotonergic clomipramine vs. noradrenergic metabolite desmethylclomipramine⁵; therefore higher drug plasma levels promote more bioavailability and enhanced selective 5-HT potency when intravenous clomipramine is used instead of oral formulation.⁵ Other hypotheses, such as the placebo effect of the intravenous route or allowing the response to oral antidepressants, have also been proposed.⁵

Usually, the starting dose is 25 mg diluted in 500 mL of NaCl 0.9%, administrated by slow infusion over 90 minutes. This can be increased to 250-300 mg by increments of 25 mg/day during 10-14 days. Monitoring of pulse, blood pressure, and electrocardiogram are essential due to potential cardiac toxicity. Other side effects present in oral formulation, such as nausea, sweating, abdominal distress or restlessness, are likewise common.

In spite of the previous period of a combined treatment with paroxetine and olanzapine, the rapid and substantial improvement after starting treatment with intravenous clomipramine may indicate the existence of a specific effect of intravenous clomipramine on Cotard's syndrome. As observed in cases of resistant-depression, this may indicate that Cotard's syndrome can be successfully treated with intravenous clomipramine, especially in situations where there is significant feed refusal and negativism. Additionally, it may be a more rapid and effective alternative to the standard oral antidepressant and antipsychotic treatment.

Despite some concerns about its side effects and toxicity, considering intravenous clomipramine as a very effective and rapid acting agent in treatment-resistant or severe cases of depression with psychotic features, such as Cotard's syndrome, raises much interest in clinical practice and needs more investigation.

References

• ¹
  Roma-Torres A. Algumas observações sobre o tratamento da neurose obsessivo-compulsiva. J Med. 1978;97:469-74.
• ²
  Kirino E, Gitoh M. Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants - a case series. Neuropsychiatr Dis Treat. 2011;7:723-8.
• ³
  Altamura AC, Dell'Osso B, Buoli M, Zanoni S, Mundo E. Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study. J Clin Psychopharmacol. 2008;28:406-10.
• ⁴
  Fountoulakis KN, Iacovides A, St Kaprinis G. Combined oral venlafaxine and intravenous clomipramine-A: successful temporary response in a patient with extremely refractory depression. Can J Psychiatry. 2004;49:73-4.
• ⁵
  Sallee FR, Vrindavanam NS, Deas-Nesmith D, Carson SW, Sethuraman G. Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial. Am J Psychiatry. 1997;154:668-73.
• ⁶
  Pollock BG, Perel JM, Nathan RS, Kupfer DJ. Acute antidepressant effect following pulse loading with intravenous and oral clomipramine. Arch Gen Psychiatry. 1989;46:29-35.

Publication Dates

• Publication in this collection
  April-June 2013

History

• Received
  5 Nov 2012
• Accepted
  2 Dec 2012