WITHANIA: A USEFUL ADJUNCT WITH ANTIPSYCHOTIC MEDICATIONS

Antipsychotic drugs are strong medicines, and while they can successfully alleviate symptoms of psychosis and prevent relapse of schizophrenia and related conditions, like all drugs they are not without side effects.

There are two types of antipsychotics, older generation ones such as chlorpromazine or haloperidol developed in the 1960s, and so called ‘atypical’ antipsychotics such as olanzapine, clozapine and quetiapine developed in the 1990s, with a different side effect profile. While atypical newer generation antipsychotics are less likely than older generation ones to produce the extrapyramidal or Parkinson’s disease-like side effects, they can cause weight gain and precipitate or worsen metabolic syndrome or diabetes, and both types increase the risk of sudden cardiac death. Over-use and mis-use of antipsychotics is also of growing concern in the elderly(1).

Despite these risks, in a world in which the incidence and predominance of mental health conditions is rising, prescribing rates for antipsychotic drugs are increasing. Nearly seven million Americans take antipsychotic medications, and a recent study revealed a 49% rise in the use of anti-psychotic drugs by New Zealanders between 2008 and 2015. New Zealanders are now 60% more likely to be prescribed such drugs than Australians, with one in 36 New Zealand adults, or 2.81% of the population, being prescribed antipsychotic medication in 2015(2).

This recent New Zealand study also suggests that in a significant and probably increasing number of cases, these strong prescription-only drugs are being used to help with stress and associated sleep problems, rather than for their primary indication for conditions such as schizophrenia and bipolar disorders. Such ‘off label’ uses for prescription-only antipsychotics such as olanzapine, is something that has landed pharmaceutical companies in court in the U.S., in a number of prominent cases.

Herbal medicine offers an array of potential treatments for insomnia and stress-related conditions(3). One of the most suitable of these is Withania somnifera (Withania), known as Ashwagandha in India. The roots of Withania have a subtle but powerful nervous system and adrenal tonic action which insulates the nervous system from stress, enabling it to be better prepared to respond appropriately to the ‘fight or flight’ response. Many studies now support its applications for stress-associated anxiety conditions, including several human clinical trials(3).

Another possible application for Withania became apparent recently, through an American clinical trial where it was used as an adjunctive treatment alongside antipsychotic drug treatment in patients with schizophrenia(4). A total of 66 patients who had recently experienced an exacerbation of their schizophrenia symptoms, were given Withania or placebo alongside their usual antipsychotic drug medications, for a 12 week period. Outcomes were change from baseline to end of treatment on the “Positive and Negative Syndrome Scale” (PANSS), which measures total, positive, negative, and general symptoms of schizophrenia, and indices of stress and inflammation.

Patients given Withania were significantly more likely to achieve at least 20% improvements in PANSS negative, general, and total symptom scores, but not positive symptom scores, compared to those assigned to placebo. They also showed a significant improvement in stress scores compared to placebo. Additionally, only two of the Withania-treated subjects required an increase in their antipsychotic drug dosage, whereas nine of the placebo-assigned subjects either had their antipsychotic drug dosage increased or had a second antipsychotic drug added. These improvements were first noted at 4 weeks, and continued through the 12-week study period.

This is not the first time that Withania has been shown to be useful when taken alongside antipsychotic drugs. A one month clinical trial involving 30 schizophrenia patients with metabolic syndrome who had taken second generation antipsychotics for more than 6 months, found that adding Withania to their normal antipsychotic medication reduced serum triglycerides and fasting blood glucose, thus improving these metabolic syndrome symptoms(5).

Apart from Withania, clinical trials have shown appropriate doses of other high quality herbal medicines to benefit patients receiving antipsychotic drugs. Ginkgo was found to both increase the response rate to haloperidol when taken alongside it for 12 weeks(6), and to reduce the incidence of extrapyramidal side effects(7, 8). Similar effects have also been reported using Ginkgo alongside olanzapine(9).

Another U.S. study has shown American Ginseng (Panax quinquefolium) to have positive effects on memory function in individuals with schizophrenia, and to reduce the occurrence of extrapyramidal symptoms in patients on antipsychotic medications(10).

While underlying reasons for the high and increasing level of antipsychotic drug use in New Zealand and other countries should be further examined and addressed, clinical trials suggest that adjunctive herbal medicines such as Withania, Ginkgo and American ginseng, can play a role to help reduce some of the adverse events, and improve their response rates. Larger and longer term trials, are warranted.

References:
1. Bjerre LE; Canadian Fam Physician 2018; 64(1):17-27
2. Wilkinson S, Mulder RT. NZ Med J 2018 Aug 17; 131(1480):61-67.
3. Rasmussen PL, Feb 2017; Why Herbs should be the first choice of treatment for acute    anxiety. http://www.herbblurb.com
4. Chengappa KNR et al, J Clin Psychiatry 2018 Jul 10;79(5).
5. Agnihotri AP et al, Indian J Pharmacol 2013; Jul-Aug;45(4):417-8
6. Zhang XY et al, Psychopharmacology 2006; 188(1):12-17.
7. Zhang XY et al, J Clin Psychiatry 2001; 62(11):878-883.
8. Chen X et al, Psychiatry Res 2015; 228(1):121-127.
9. Atmaca M et al, Psychiatry Clin Neurosci 2005; 59(6):652- 656.
10. Chen EY et al, Phytother Res. 2012 Aug;26(8):1166-72

Advertisements