ME Association Statement: Aripiprazole (Abilify) & ME/CFS

May 25, 2021


We received reports that a small number of people with ME/CFS in the UK and overseas are apparently being prescribed or are obtaining an antipsychotic drug called Aripiprazole (trade name = Abilify) and using it as a treatment for ME/CFS.

We issued a rapid statement of concern on social media last week and this was updated to take account of additional information and some of the comments and queries that were raised during the discussion that ensued most notably on MEA Facebook.

The ME Association does not recommend that anyone with ME/CFS attempts to obtain or to take this drug, even in small doses, until such time as more appropriate research – double-blind placebo controlled clinical trials – can better determine safety and efficacy.

Even with supportive trial evidence, the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE) would need to approve its use before it can be prescribed to treat ME/CFS. To take this drug at this time poses a significant potential risk to health.

We understand the desperation that exists in this community; many of us have ME/CFS and share this desperation too. It can be very hard to watch as others claim they have found something – particularly a drug – that helps relieve symptoms. But we need to be cautious and to wait until such time as strong evidence of efficacy and of safety is found.

Aripiprazole should be approached with at least as much caution and with as much of a critical eye as we have in the past applied to personal anecdotes and even to research relating to Rituximab for example, or the Lightning Process and Graded Exercise Therapy.

Unfortunately, given our current state of knowledge about ME/CFS, there is no quick fix, silver bullet or magic cure. We remain vigilant and welcome any grant application from researchers who are considering clinical trials involving Aripiprazole or any other potential treatment for this devastating medical condition.

Background

Aripiprazole (trade name = Abilify) is a prescription-only antipsychotic drug that can be used to treat schizophrenia, bipolar disorder, and major depressive illness. It is also sometimes used to treat irritability associated with autism. Aripiprazole is not licensed to treat ME/CFS.

As with other antipsychotic drugs, aripiprazole affects the levels of chemical transmitter systems in the brain and nervous system – especially those involving dopamine and serotonin.

It is being claimed that Aripiprazole has a different pharmacological effect on brain chemical transmitters at lower doses and that this could have a beneficial effect in ME/CFS – possibly due to a modulatory effect on neuroinflammation and microglial activation – but there is no sound scientific evidence at present to support this theory in ME/CFS.

Although there are some anecdotal reports appearing on the internet from people with ME/CFS who claim to have used this drug and who say that it has been beneficial, other people are reporting that they have had significant problems with side-effects.

There have not been any clinical trials to assess whether this drug could be a safe and effective treatment for ME/CFS. The only report on the use of this drug in the medical literature is a retrospective case study that reviewed the medical records of 101 people with ME/CFS. This research while interesting is of low quality and not an example of the kind of clinical trial that would be required before approval could be sought from the MHRA and NICE.

I have seen this retrospective study [above] and it does indicate that this is a drug that could be of benefit – possibly to a sub-group of people with ME/CFS. However, the only way to proceed with assessing a drug like this that is capable of causing very severe adverse reactions is though a very well conducted placebo controlled clinical trial that involves doctors with good experience in the use of anti-psychotic drugs.

In our current state of knowledge it is not something that people should be asking their GP to prescribe. And I would be very surprised if any GP would be willing to do so – given the legal consequences if something did go wrong.

Dr Charles Shepherd, ME Association Facebook Comment

Side-effects

Aripiprazole has a large number of common and potentially very serious side-effects – many of which overlap with ME/CFS symptoms.

Common or very common

anxiety; appetite abnormal; diabetes mellitus; fatigue; gastrointestinal  discomfort; headache; hypersalivation; nausea; vision disorders

Uncommon

Depression; hiccups; hyperglycaemia (increased blood sugar levels); sexual dysfunction

Frequency not known

Aggression; alopecia (hair loss); cardiac arrest; chest pain; diabetic hyperosmolar coma; diabetic ketoacidosis; diarrhoea; dysphagia (difficulty swallowing); generalised tonic-clonic seizure; hepatic/liver disorders; hyperhidrosis (increased sweating); hypertension; hyponatraemia (lowered sodium level); laryngospasm (increased blood pressure); musculoskeletal stiffness; myalgia (muscle pain); oropharyngeal spasm (throat spasm); pancreatitis (inflammation of the pancreatic gland); peripheral oedema (fluid retention); photosensitivity reaction (sensitivity to light); pneumonia aspiration; rhabdomyolysis; serotonin syndrome; speech disorder; suicidal behaviours; syncope; temperature regulation disorder; thrombocytopenia (low level of blood platelets); urinary incontinence; weight decreased.

MHRA/CHM advice

Clozapine and other antipsychotics: monitoring blood concentrations for toxicity (August 2020)

Following fatal cases involving toxicity of clozapine and other antipsychotic medicines, the MHRA advises that monitoring blood concentration of Aripiprazole may be helpful in certain circumstances, such as patients presenting symptoms suggestive of toxicity, or when concomitant medicines may interact to increase blood concentration of aripiprazole.

Two important safety points if anyone is being prescribed this drug:

1. It is advisable to monitor the blood level of a hormone called prolactin at the start of therapy, at 6 months, and then yearly.

This is because people taking antipsychotic drugs not normally associated with symptomatic hyperprolactinaemia (raised level of prolactin) should be considered for prolactin monitoring if they show symptoms of hyperprolactinaemia (such as breast enlargement and galactorrhoea)

2. There is a potentially life-threatening side-effect with these sort of antipsychotic drugs known as neuroleptic malignant syndrome.

Warning signs include muscle stiffness, high temperature, increased heart rate, sweating and rapid breathing.

Urgent medical attention should be sought if this is suspected.

Conclusion

Whilst using a low dose may reduce the incidence and severity of side-effects, this can only be confirmed through assessment in properly conducted clinical trials.  

It should also be noted that people with ME/CFS are often very sensitive to any drug that acts on complex chemical transmitter systems in the brain, including serotonin, even at very low doses.

Idiosyncratic reactions, which are unpredictable and not explained by the pharmacologic properties of the drug, can also occur. 

Whilst there are some interesting reports of benefit, there are also some very disturbing reports from people who have experienced a bad reaction to this drug.

We need evidence on both safety and efficacy from well conducted clinical trials – including dose response studies – before any conclusions about the possible use of Aripiprazole in ME/CFS can be made.

In our current state of knowledge, and in the absence of information on safety and efficacy from clinical trials in relation to MECFS, this is not therefore a drug that should be prescribed for the treatment of ME/CFS outside a clinical trial.

This is a situation where doctors should be following one of the cardinal rules of practicing medicine: Primum non nocere – First, do no harm. It is consistent with the recommendations in the 2020 ‘First Do No Harm’ report of the Independent Medicines and Medical Devices Safety Review.

Dr Charles Shepherd, Hon Medical Adviser, ME Association

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