Tamoxifen Significantly Reduces Mania Symptoms
A recent trial of the drug Tamoxifen with patients who were experiencing mania, or who were in a mixed state that included mania as a component, significantly reduced the symptoms of mania in nearly half the sample.
Tamoxifen is normally associated with the treatment of breast cancer but its action is to inhibit a group of enzymes known as protein kinase C. This has relevance to bipolar disorder as abnormal activity by these enzymes is know to affect judgments, problem-solving, disorganization in thinking and distractibility.
Dr Aysegül Yildiz, of the Dokuz Eylül University Medical School, Izmir, Turkey, conducted a small clinical trial on 66 patients aged 18-60. All the patients were diagnosed with bipolar disorder and all were in a manic state during the drug trial. The team of researchers randomly allocated the patients into one of two experimental conditions. Those in the first condition were asked to take tamoxifen and those in the second condition received placebo. All patients received lorazepam to help with the control of symptoms.
The trial lasted for three weeks. Of the 66 patients who started, 16 dropped out. Twenty nine patients completed the tamoxifen condition and 21 the placebo condition. At the end of the drugs trial it was clear that those who had taken tamoxifen scored significantly lower on tests used to measure the severity of mania. Nearly half the patients (48%) in the tamoxifen condition responded positively to the drug and 28 per cent of these had mania scores so low that they were considered to be in remission. It was also noted that patients in the tamoxifen condition used less lorazepam during the trial (an average of 25 mg compared with 42 mg).
This is not the first time that the positive effects of tamoxifen have been noticed during a clinical trial. Researchers at the National Institute of Mental Health (NIMH) conducted a similar three week trial but with fewer numbers of participants (16 in total). Patients taking tamoxifen responded positively by the fifth day. What this latest research proves is that tamoxifen directly blocks the effects of protein kinase C and gives a fairly speedy therapeutic effect compared with some of the more standard medications.
It is known that the risk of developing bipolar disorder is influenced by a gene called DGKH. This gene is responsible for the production of a protein kinase C regulating protein. One problem of using tamoxifen to further block the protein is that it also blocks estrogen and this is the reason tamoxifen is effective in the treatment of breast cancer.
In an editorial relating to the Turkish trial, Mauricio Tohen, M.D., states that, “ the role of tamoxifen per se in the treatment of bipolar disorder still remains to be determined, but its anti-estrogen effects are likely to represent a safety challenge”. However, the body of evidence now developing does seem to represent an interesting development towards the treatment of mania.