Hormone patch for schizophrenia

“A hormone patch may protect women with schizophrenia or other severe mental illnesses from psychotic feelings”, BBC News reported. It said that scientists had found that giving women oestrogen made them less likely to report suffering hallucinations or delusions.

The story is based on a study in 102 women with schizophrenia, half of whom wore a daily patch of estradiol, the most common form of oestrogen, for four weeks. As the researchers acknowledge, this is a small study and much further research in a greater number of women, and over a longer period of time, is needed to look at the effectiveness of this treatment alongside other standard treatments. Most importantly, future studies will need to consider the long-term safety implications of giving women a high concentration of unopposed oestrogen (i.e. not combined with a progestogen hormone, as in the contraceptive pill) for long periods of time.

Where did the story come from?

Dr J Kulkarni and colleagues from The Alfred Hospital, Monash University’s School of Psychology, Psychiatry and Psychological Medicine and Monash Medical Centre, Melbourne, Australia, carried out the research. Funding was provided by the Stanley Medical Research Institute and the National Health and Medical Research Council of Australia. The study was published in the peer-reviewed medical journal: Archives of General Psychiatry.

What kind of scientific study was this?

This was a double blind randomised controlled trial designed to look at the effects on psychotic symptoms in women with schizophrenia of applying either an oestrogen patch or placebo patch to the skin, alongside standard treatment.

The researchers recruited 102 women to the study from inpatient and outpatient units of two hospitals in Melbourne. All women had verified diagnoses of schizophrenia or a related schizophrenia type condition and all were diagnosed to have severe illness, including some who had not responded to previous treatments. The researchers excluded those women with a bipolar subtype of illness (although they included those with a depressive subtype), those currently receiving hormone treatment such as the pill, those pregnant or breastfeeding, those around the time of menopause, those with overactive thyroid and any with an unstable medical condition.

The women were randomly assigned to receiving either a 100 microgram per day oestrogen patch (56 women) or a placebo patch (46 women) for four weeks. Neither the women or the research team were aware of which treatment they were receiving. Other antipsychotic medications were continued. The researchers used a recognised assessment scale (Positive and Negative Syndrome Scale; PANSS) to look at psychotic symptoms at the start of the study and then once weekly for four weeks. On this scale, positive symptoms include such things as hallucinations, delusions, disorganised thinking, negative symptoms include things such as reduced emotional response, emotional and social withdrawal; and general symptoms are things like anxiety, depression, and poor control of impulses. Side effects of treatment were assessed at each follow up, and blood samples were taken to look at hormone levels at the beginning and end of the study. Statistical tests were used to look at differences in symptoms and side effects between the groups.

What were the results of the study?

In all, after some dropouts and exclusions, 85.3% of the 102 women were analysed at the end of the study (91% of the treatment group and 78% of the placebo). There were no differences between the women in either group in terms of age, severity or duration of illness, medication used, or menstrual cycle phase at the beginning of the study. Compared to the placebo group, women who received oestrogen had significantly greater improvement over time in overall symptoms, and also in positive symptoms (as measured with the PANSS total score, positive symptom score and general psychotic symptom score). There was no difference between the groups in negative symptoms as measured on the PANSS. There was no difference in rate of adverse side effects between the groups.

What interpretations did the researchers draw from these results?

The researchers concluded that the addition of 100 micrograms of oestrogen, delivered via a patch to standard treatment, significantly reduced positive and general psychotic symptoms during the four-week trial compared to standard treatment alone.

What does the NHS Knowledge Service make of this study?

This is a well-designed and carefully conducted randomised controlled trial into the effects of adding oestrogen to standard treatment for schizophrenia. However, the results must be considered in context:

• This was a small trial of only 102 women with schizophrenia disorders who fulfilled specific criteria. Further research will be needed in much larger groups of women and in those with different severities of condition and comorbidity (other conditions that they have as well as schizophrenia), to get a clearer indication of whether treatment does significantly improve symptoms.
• The duration of the trial, at four weeks, is very short. Much longer trials will be needed to look at longer-term effects and, most importantly, to consider the long term safety implications of daily giving women a high concentration of oestrogen. The oestrogen used in this patch was at a much higher concentration that that given in standard contraceptive treatment. It is also not combined with the protective effects of a progesterone hormone as in the contraceptive pill. Higher concentrations of such unopposed oestrogen are likely to make the risk of known complications of oestrogen treatment (e.g. deep vein thrombosis, high blood pressure) greater. Also in this context, there are a number of women for whom oestrogen treatment may not be suitable at all, such as those with risk factors or family history of blood vessel disease, those with migraine or liver conditions, and those who are  overweight or smoke heavily.
• Hormone treatment does carry the risk of known side effects, such as depression, nervousness or irritability symptoms, and these must be considered given the context of this disease. The implications upon the reproductive cycle and personal relationships must also be considered (for example the possibility of women assuming this as contraception and therefore engaging in unsafe sexual activity).
• No assumptions can be made from this study about the effects of isolated hormone treatment, without standard treatment being given alongside.

Further research is awaited.