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Use of thioridazine in palliative care patients with troublesome sweating

      To the Editor:
      Sweating can be a troublesome and difficult symptom to manage in patients with advanced malignancy. There are many reasons attributed to sweating in this group of patients, including sepsis, neoplastic fever, sex hormone deficiency, and drugs.
      • Mortimer P.S.
      Management of skin problems. Sweating.
      Treatment of the sweating depends on the cause. When the cause is paraneoplastic, treatment can be particularly difficult.
      • Grond S.
      • Zech D.
      • Diefenbach C.
      • Bischoff A.
      Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic.
      In hospice patients, a study described the prevalence of sweating to be 16%.
      • Quigley S.C.
      • Baines M.
      Descriptive epidemiology of sweating in a hospice population.
      Suggested treatments include nonsteroidal anti-inflammatory drugs (NSAIDs),
      • Tsavaris N.
      • Zinelis A.
      • Karabelis
      • et al.
      A randomized trial of the effect of three non-steroidal anti-inflammatory agents in ameliorating cancer-induced fever.
      but another study reported that 36% of patients who developed sweating were already on NSAIDs.
      • Quigley S.C.
      • Baines M.
      Descriptive epidemiology of sweating in a hospice population.
      Among hospice patients, sweating is attributed to opioid therapy and it has been suggested that opioid rotation does not improve sweating.
      • Zyclicz Z.
      • Krajnik M.
      Flushing and sweating in an advanced breast cancer patient relieved by olanzapine.
      In our hospice, we studied the effect of an anti-muscarinic drug, thioridazine, on the symptom of sweating. There were ten patients commenced on thioridazine for sweating during a one-year period. The ages of the patients ranged from 35–80 years (mean 61 years). All of them suffered from advanced malignancy. Five were male and five were female. They were begun on thioridazine 10 mg at night. Five of them had their dose increased to 25 mg by the fourth day. Seven of them reported that their sweating improved significantly in response to the treatment. This improvement was directly related to an improvement in their well being.

      1. Comment

      Thioridazine is a phenothiazine, antipsychotic, anti-muscarinic drug that has been used in the treatment of sweating.
      • Regnard C.
      Use of low dose thioridazine to control sweating in advanced cancer.
      • Cowap J.
      • Hardy J.
      Thioridazine in the management of cancer related sweating.
      Concerns have been raised that thioridazine is associated with cardiotoxicity more commonly than other neuroleptics.
      • Buckley N.A.
      • Whyte I.M.
      • Dawson A.H.
      Cardiotoxicity more common in thioridazine overdose than with other neuroleptics.
      In the United Kingdom, it is only licensed for the second-line treatment of schizophrenia. It is contraindicated in patients with clinically significant cardiac disorders, QT prolongation on ECG, history of ventricular arrhythmias or torsades de pointes, bradycardia or second or third degree heart block, uncorrected hypokalemia or hypomagnesemia, and concurrent treatment likely to increase thioridazine levels or increase QT interval.

      Antipsychotic drugs. Section 4.2.1. British National Formulary 46; British Medical Association and the Royal Pharmaceutical Society of Great Britain. London, 2003.

      In palliative care settings, use of drugs that would be relatively contraindicated with thioridazine is relatively limited. A prospective trial of 600 individuals showed that antipsychotic drugs cause QT interval lengthening in a dose-related manner,
      • Reilly J.G.
      • Aysis S.A.
      • Ferrier I.N.
      • et al.
      QTc-interval abnormalities and antipsychotic drug therapy in psychiatric patients.
      and the authors concluded that age over 65 years; use of thioridazine, tricyclic antidepressants and droperidol; and antipsychotic dose were the robust predictors of a prolonged QT interval. It has also been reported, however, that although prolonged QTc is relatively common (16%) in patients referred to a specialist palliative care clinic, severely prolonged QTc is rare (0.7%).
      • Walker G.
      • Wilcock A.
      • Carey A.M.
      • et al.
      Prolongation of QT interval in palliative care patients.
      In the latter study, presence of coexistent cardiac disease or high level of alkaline phosphatase were identified as robust associated features of prolonged QTc.
      Low dose thioridazine is well tolerated and has balanced anti-muscarinic effect.
      • Zyclicz Z.
      • Krajnik M.
      Flushing and sweating in an advanced breast cancer patient relieved by olanzapine.
      This suggests that thioridazine, when used with clinical consideration of contraindications and cautions, is a drug worth considering for troublesome and exhausting sweating in palliative care patients, as supported by our experience.

      References

        • Mortimer P.S.
        Management of skin problems. Sweating.
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        • Zech D.
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        • Bischoff A.
        Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic.
        J Pain Symptom Manage. 1994; 6: 372-382
        • Quigley S.C.
        • Baines M.
        Descriptive epidemiology of sweating in a hospice population.
        J Palliative Care. 1997; 13: 22-26
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        • Karabelis
        • et al.
        A randomized trial of the effect of three non-steroidal anti-inflammatory agents in ameliorating cancer-induced fever.
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        Flushing and sweating in an advanced breast cancer patient relieved by olanzapine.
        J Pain Symptom Manage. 2003; 25: 494-495
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        Use of low dose thioridazine to control sweating in advanced cancer.
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        • Hardy J.
        Thioridazine in the management of cancer related sweating.
        J Pain Symptom Manage. 1998; 15: 266
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      1. Antipsychotic drugs. Section 4.2.1. British National Formulary 46; British Medical Association and the Royal Pharmaceutical Society of Great Britain. London, 2003.

        • Reilly J.G.
        • Aysis S.A.
        • Ferrier I.N.
        • et al.
        QTc-interval abnormalities and antipsychotic drug therapy in psychiatric patients.
        Lancet. 2000; 355: 1048-1052
        • Walker G.
        • Wilcock A.
        • Carey A.M.
        • et al.
        Prolongation of QT interval in palliative care patients.
        J Pain Symptom Manage. 2003; 26: 855-859