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

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Why Herbs Should Be the First Choice of Treatment for Acute Anxiety

Anxiety can manifest in a wide range of ways. Apart from the internal emotional fearfulness, symptoms can include irritability, agitation, muscle tension, palpitations, sweating, insomnia, breathlessness, poor concentration, reduced socialisation and ability to undertake everyday activities. It is the most prevalent mental health disorder affecting children and adults, but many more people are dealing with problematic anxiety symptoms without any diagnosis.

In our increasingly changing world, where our daily exposure to stressful stimuli and life challenges can produce a rising barometer of worries, anxiety is often a major impediment to leading a fulfilling and happy life. Like most other health woes, humans have long pursued various practices to help overcome anxiety, the most popular of which is alcohol. Then there are drug medications, which have long been used to relieve anxiety, and remain widely prescribed.

Barbiturates were the first of these, sedative and anticonvulsant drugs which became popular particularly with sleep-deprived young mothers in the middle of last century, but which lead to the overdose deaths of thousands of people, including Elvis Presley and Marilyn Monroe. The next day ‘hangover effect’ from barbiturates was also always a problem, and development of a new chemical group of anxiolytic (anti-anxiety) and sedative drugs known as the benzodiazepines, lead to these superceding the barbiturates for the treatment of anxiety and insomnia. Benzodiazepines seem to act predominantly through stimulating GABA (gamma amino butyric acid) receptors in the central nervous system, and the commercialisation of Valium® (diazepam) by Roche in 1963 marked the start of a period during which this and other benzodiazepine drugs such as lorazepam, alprazolam and clonazepam began to be widely prescribed by GP’s and psychiatrists for anxiety and sleep difficulties. Between 1969 and 1982 Valium® was the most prescribed drug in the U.S., during which time Roche’s share price soared.

While safer than barbiturates, and effective as a ‘quick fix’ for anxious feelings or insomnia, safety concerns for benzodiazepines soon emerged. Feelings of fatigue, or a hangover the following day when taken as sleeping tablets, and a wide range of other side effects are all too common experiences. Most significant of these is the development of tolerance when they are used for more than a short period of time. As anyone who has been through it will testify, withdrawing from long term benzodiazepine use is a hugely stressful, unpleasant and often very protracted experience.

Feelings of depression can both contribute to or arise from excessive anxiety, and it is not uncommon for feelings of low mood and a low tolerance to stress, to be experienced together with anxiety. Apart from GABA, neurotransmitters such as serotonin, adrenaline and dopamine are intrinsically involved in influencing our emotions and mood, interacting together in complex ways that scientists still have little understanding of. It is therefore not surprising that many SSRI’s (selective serotonin reuptake inhibitor) drugs, used primarily as antidepressants, can have an anxiolytic effect in some people, and in many countries, these are often prescribed instead of or together with benzodiazepines, for anxiety conditions.

While sometimes effective as anxiolytics and less likely to produce adverse effects than most older generation tricyclic antidepressants, some find that SSRI’s can cause or increase anxiety feelings, or experience any one or more of a wide range of unpleasant side effects including insomnia, weight gain, emotional numbing or sexual dysfunction.

Another class of non-benzodiazepine sleeping tablets, the so-called  ‘Z-drugs’ such as zopiclone and zolpidem, have become popular in recent years, and while initially thought to be less habit-forming than benzodiazepines, they can also be very difficult to withdraw from after more than short-term use.

A large number of herbs have been traditionally used for nervous conditions and their anxiolytic effects, several of which have been shown in clinical trials to be beneficial as anxiety treatments. These include Chamomile, Skullcap, Passionflower, Valerian, Kava, Lemon balm and Withania.  Despite the number of well-designed trials undertaken to date being relatively low, and results sometimes variable depending on the particular herbal product(s) and dosages used, results are encouraging and in all cases show a better safety profile than for comparable anxiolytic drugs.

Of these, Kava (Piper methysticum), is the most studied, and is a non-addictive anxiolytic with great potential to treat anxiety. Its effectiveness in treating anxiety has been affirmed through several clinical trials and meta-analysis(1-3). While case reports of liver toxicity associated with kava usage lead to its restriction in some countries at the end of last century, use of the wrong plant part as raw material, or use in combination with alcohol or various drugs, were likely contributory factors. Also the frequency of such adverse events reports was substantially less than that for paracetamol, a commonly used analgesic.

Aerial parts of the herb Passionflower (Passiflora incarnata), have also been taken for anxiety for many centuries, and in a trial involving 36 outpatients with generalized anxiety disorder, it was as effective as the benzodiazepine drug oxazepam, but unlike oxazepam caused no impairment of job performance(4).

Roots of the herb Withania (Withania somnifera, Ashwagandha), have a subtle but powerful nervous system and adrenal tonic action, which insulates the nervous system from stress, and enables the adrenal glands to be better prepared to respond appropriately to stressful stimuli. A large number of scientific papers now support its applications for stress-associated anxiety conditions, including several recent human clinical trials(5,6).

While further studies involving greater participant numbers and longer term treatment are needed to identify optimal dosages and phytochemical makeup of the treatments involved, the fact that most herbal anxiolytic agents are safe and have the same or only a slightly higher incidence of adverse effects to placebo, is clear. It is therefore logical that before reverting to drug medications, more likely to produce unwanted adverse effects and in some cases long term dependency, herbal anxiolytics should be tried, in anxiety conditions.

Refs:

  1. Sarris J, Aust NZ J Psychiatry 2011; 45(1):27-35.
  2. Sarris J, J Clin Psychopharmacol 2013; 33(5):643-648.
  3. Savage K et al, Trials 2015; 16:493.
  4. Akhondzadeh S et al, J Clin Pharm Ther 2001; 26(5):363-367.
  5. Chandrasekhar K et al, Indian J Psychol Med 2012; 34(3):255-262.
  6. Pratte MA et al, J Altern Complement Med 2014; 20(12):901-908