Levothyroxine Augmentation in Clozapine Resistant Schizophrenia: A Case Report and Review (2015)

Levothyroxine Augmentation in Clozapine Resistant Schizophrenia: A Case Report and Review

There are many reports that show different thyroid abnormalities in schizophrenia without clear establishment of their role in etiology and treatment outcome of schizophrenia. Among these reports, there are only a few that consider a role for thyroid hormones as augmenting agents in the treatment with antipsychotic drugs. This case report outlines symptom subsidence of a patient with clozapine refractory paranoid schizophrenia and normal thyroid function who added levothyroxine to clozapine and found that symptoms of psychosis returned once levothyroxine was discontinued. Although this observation needs to be confirmed in controlled clinical trials, we aimed to discuss possible hypothesized mechanisms underlying this observation.

“The patient was hospitalized with a confirmed diagnosis of refractory paranoid schizophrenia, and clozapine was administered with a gradually increasing dose, up to 600 mg per day. After six weeks, she was significantly calmer with lower anxiety and aggression, her sleep quality had improved, and her appetite had increased. However, she was still experiencing social withdrawal, persecutory and reference delusions, and visual hallucinations. Despite good drug adherence, psychosis continued four months after discharge. Afterwards, without our knowledge, the mother, who had hypothyroidism, advised the patient to use levothyroxine (at a dose of 0.1 mg per day) in addition to clozapine. After two weeks with this treatment, hallucinations and delusions completely subsided, and the patient’s social relations improved. When we were informed, discontinuation of levothyroxine was advised, given her normal thyroid tests. About three weeks after the removal of levothyroxine, psychosis symptoms gradually reappeared (despite still taking clozapine). The patient was again experiencing hallucinations and delusions.”

“About 30–36% of patients with chronic schizophrenia have abnormal thyroid tests, but, in clinical terms, they are euthyroid. These abnormalities may disappear following successful treatment of schizophrenia and may also have a correlation with treatment response to antipsychotics. For instance, it has been observed that higher T3 serum levels in patients with chronic schizophrenia are related to their better cognitive functions and lower extrapyramidal drug side effects. It has also been seen that high basal TSH is associated with poorer response and blunted TSH response to thyrotropin releasing hormone (TRH) and a high level of T4 before treatment with better response to treatment. T4 levels before treatment are also positively correlated with severity of the disorder. Although the results of studies are contradictory, they mostly cite increased total and free T4 in patients with schizophrenia before treatment and their normalization after treatment”

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