Doses of Clomipramine for OCD

By | January 23, 2015

Prescribing clomipramine (trademarked as Anafranil and Clofranil) for patients with obsessive-compulsive disorder requires consideration of not only the nature of the drug but also the nature of the disorder. On the one hand, it has been our clinical experience that patients with obsessive-compulsive disorder are incredibly tolerant of side effects (see case examples at the end of this chapter). Perhaps this is because, as the patients themselves express it, they have suffered with their illness, often in secret, for so long that the improvement in their symptoms and in their overall level of functioning is well worth any side effects. On the other hand, the nature of the illness means that these patients experience a great deal of doubt and apprehension; they might obsess over actually taking the medicine at all and may require considerable encouragement and repeated explanation of its side effects. These patients can often worry excessively about the possible side effects, often imagining the worst possible scenario; therefore, they need considerable reassurance. In the initial phases of treatment, doctor availability and a slow, gradual increase in dose are particularly important in terms of the patient’s long-term compliance. Although several effective treatment modalities are available for treating obsessive-compulsive disorder (OCD), early rejection of the medication by the patient should be avoided because it will delay overall improvement.

Anafranil (clomipramine hydrochloride) is available as capsules of 25, 50, and 75 mg for oral administration.

Unfortunately, no specific data are available on which patients respond best to clomipramine versus other antiobsessional agents. However, in a preliminary report, it seems that a great deal of overlap exists between fluoxetine and clomipramine response (). A few studies have addressed which symptoms seem most resistant to pharmacotherapy In 1988, Eisen and Rasmussen reported that among patients with psychotic features and obsessive-compulsive disorder (OCD), those with a paranoid or obsessional quality to their delusions had a better prognosis than did those with magical thinking or schizophrenia as part of their psychotic features. Ackerman et al. (1994) showed a better clomipramine treatment response in patients with lower Hamilton Rating Scale for Depression (Ham-D; Hamilton 1960) scores or late age of onset, whereas Alarcon et al. (1993) found a correlation between poorer response to clomipramine with higher initial Y-BOCS scores or presence of cleaning rituals.

The starting dose of clomipramine should be low — 25-50 mg the initial day — because there have been some reports of acute onset of nausea and vomiting requiring discontinuation (). Doses can then be increased every 1-3 days by another 25-50 mg until a maximum dose of 250 mg is reached or until side effects become intolerable. Most studies have employed doses in the range of 75-300 mg (A cautionary note must be made about using clomipramine at doses greater than 250 mg. The CIBA-Geigy Corporation has released a warning indicating an increased instance of seizures in patients with a dose of 300 mg or more (2.1% [10 of 472 patients] versus 0.48% [12 of 2,514 patients] at doses of 250 mg or less). Thus, CIBA-Geigy has restricted the maximum dose to 250 mg/day). Because no reports have been made of dose findings with clomipramine in obsessive-compulsive disorder (OCD), we need to count on “accumulated clinical experience.” Although some patients have shown responses at doses as low as 75 mg, traditionally a dose in the range of 150-250 mg seems to be most effective. We usually choose once-daily dosing at bedtime to allow for better compliance. In addition, we have found that this approach minimizes the side effects in many cases and that there are fewer complaints of sedation, one of the major side effects of clomipramine. Occasionally, patients cannot tolerate 200 or 250 mg of clomipramine at once, in which case the dose is split and given twice a day, once in the morning and once at bedtime, with the smaller dose (e.g., 100 mg) given in the morning to minimize daytime sedation.

When considering clomipramine, as when prescribing any TCA, therapists should use their clinical judgment and take into account differences in age response and dosing (). We have some clinical experience with patients in their early 60s, most of whom were women weighing approximately 100 lb for whom 75-150 mg was sufficient rather than the 250 mg we give most patients initially. In general, elderly patients may be able to get by with a smaller dose; they may, in fact, not tolerate the larger dose. Because elderly patients are more prone to side effects, clinicians must be cognizant of several points when considering clomipramine:

  1. 1) Elderly patients are more prone to orthostatic hypotension and dizziness, which can result in falling when getting out of bed and can increase the risk of hip fracture. Therefore, clinicians should ask about these symptoms, check for orthostatic hypotension, and explain to the patient that he or she needs to be very careful when getting out of bed. It is suggested that patients rise from a reclined position first to a seated position on the edge of the bed and then stand slowly, watching for dizziness. If this alone does not help the orthostatic hypotension and dizziness, then a lower dose should be considered.
  2. 2) Constipation as a side effect can result in fecal impaction or hemorrhoids; again, if the symptom is severe, lower the dose and/or add a stool softener or prune juice.
  3. 3) Another side effect is a nondescript type of mental cloudiness that some patients describe as “not thinking as clearly or quickly” or as “being forgetful.” Decreasing the dose or a trial off medication may be helpful in making the differential diagnosis between this side effect and dementia.
  4. 4) Dehydration is likely to increase drug serum levels and make the patient toxic; if an elderly patient becomes ill and dehydrated, the dose may need to be decreased until the patient rehydrates.
  5. 5) Elderly patients are often taking other medications. Any potentially harmful interactions, such as risk of cardiac arrhythmias, should be assessed before starting clomipramine and should be monitored throughout treatment.

Selections from the book: “Current treatments of obsessive-compulsive disorder” (2001).