RxISK

Making Medicines Safer for All of Us

Side Effects of Antipsychotics

Author: Dr. David Healy

Last updated: 2016

For the most part, antipsychotic side effects will clearly seem like side effects. There are, however, a number of effects brought on by the drugs that may seem more like a worsening of the illness. It is important that you are able to tell the difference. All too often, both takers and prescribers can mistake some of the problems caused by treatment for features of illness.

Some side effects can resemble Parkinson’s disease, particularly where they involve abnormal movements. This is because antipsychotics reduce dopamine activity in the brain, and Parkinson’s disease involves lowered dopamine. However, antipsychotics do not cause Parkinson’s disease.

Dopamine system side effects:

Non-dopamine side effects:

Abnormal movements

Abnormal movements (dyskinesias) are one of the most noticeable features of Parkinson’s. The pill-rolling tremor of the hand is perhaps the most common. When caused by antipsychotics, this tremor will be experienced as anything from a hardly noticeable fine tremor to a clear shake that makes coordination difficult. This can seriously interfere with social life.

The most common set of abnormal movements affects the hands or arms, but the legs or even the entire body may be affected.

There may be abnormal movements of the mouth and face such as repetitive pouting of the lips and protrusion of the tongue. The jaw may be affected, leading to tooth-grinding and dental problems.

The respiratory muscles can become discoordinated resulting in wheezing or shortness of breath. This may be persistent or it may occur in episodes – happening only at night for instance. It may be misinterpreted as asthma or a panic attack, and the treatments given may make the problem worse.

Also see Tardive Dyskinesia.

Abnormal muscle tone

Abnormal muscle tone (dystonia) may be experienced as spasms – these are sudden and involuntary muscle contractions. However, the problem is more commonly experienced in the less obvious form of pain. Treatment should involve changing drug, rather than painkillers.

When the mouth or larynx (voicebox) is affected, there can be difficulties speaking clearly or difficulties with eating or drinking. It may also lead to a change in voice, so that the person sounds hoarse.

Although relatively rare, the eyeballs may roll up in the head so that only the whites of the eye can be seen, in what is called an oculogyric crisis. The person affected can see almost nothing. The first time this happens, the individual concerned and anyone else watching may be very alarmed. The spasm will usually wear off inside an hour. It can also be quickly reversed by an anticholinergic antidote.

Other problems include lockjaw (trismus) and clenching of the jaw, especially at night, which can lead to dental problems.

Aggression and impatience

It is unclear whether this is solely due to feelings of restlessness from akathisia, or whether there is a separate mechanism involved. While there are no clinical trials showing that antipsychotics cause aggression or impatience, drug companies clearly believe this can happen and have listed it as a side effect on the package insert of most of these drugs.

Akathisia (restlessness, agitation & turmoil)

Akathisia may be one of the most serious side effects of antipsychotics. This is a complex, unpleasant, emotional state that often (though not always) leads to visible restlessness.

The best word from the sufferer’s point of view to describe what is happening is probably mental turmoil. Restlessness does not cover all that may be involved. It can sometimes include the emergence of strange and unusual impulses, often of an aggressive nature.

In healthy volunteer trials, some participants who were given an antipsychotic and asked to perform tests found it almost impossible to remain in the room, but at the same time found it very difficult to explain what was wrong.

Many psychiatrists who have tried antipsychotics have experienced akathisia, and a number have said it was close to the worst experience of their lives.

See our main page on akathisia.

Anticholinergic effects

Anticholinergic effects are a group of side effects caused by actions on a neurotransmitter called acetylcholine. They happen in a variety of different medications.

A number of antipsychotics can produce prominent anticholinergic effects, including:

  • Blurred vision
  • Dry mouth
  • Nasal drying

Mild anticholinergic effects usually wear off with time. If they are causing significant discomfort and do not clear up after a few days, the drug should be changed or discontinued.

Bed-wetting

It is important to be aware of unusual side effects (with all drugs) that may not typically be listed. For example, an unusual problem on clozapine is bed-wetting.

Cardiovascular conditions

Palpitations

Palpitations are an awareness that the heart is beating harder than normal, or that it is beating irregularly, which may feel like fluttering in the chest. Palpitations are usually harmless.

Effects on heart rhythm

Almost all antipsychotics and antidepressants can affect the electrical conduction of the heart, especially by lengthening the QT interval, which in severe cases can be fatal.

It may be a problem if:

  • The dose is increased
  • The person was born with a longer QT interval to begin with
  • The person is on a combination of drugs where each drug has this effect, leading to a dangerous increase

Inflammation and excessive growth of heart muscle

Clozapine and some other drugs in the group appear to cause a myocarditis (an inflammation of the heart muscle) that can be fatal. This is most likely to happen in the first few weeks of treatment. Clozapine has also been linked to cardiomyopathy (an excessive growth of cardiac muscle), which can appear after months or years of treatment when it shows up as heart failure. These problems are relatively uncommon.

Blood clots

Antipsychotics are associated with a 6-fold increase in the risk of blood clots (thrombosis), which is particularly likely to be a hazard in those who are older or who are immobilized for one reason or another, or in those on contraceptives or other treatments that increase the risk of thrombosis.

Cardiorespiratory failure

Antipsychotics as well as drugs used to treat Parkinson’s disease can cause cardiorespiratory failure through their effects on dopamine, which has a role in regulating breathing and cardiac function. This may be a particular hazard in the elderly.

Catatonia

Catatonia is a state in which a person’s perceptions and free will are cut off from movement. The person may look like they are responding to visual or auditory stimuli, when in fact they aren’t. They might not be communicating at all, or they may be repeating words, phrases or gestures. The usual response is to assume that they are psychotic and increase the dose of the antipsychotic, when in fact the problem is being caused by the drug.

Catatonia is closely related to Neuroleptic Malignant Syndrome (NMS).

Diabetes

In addition to causing weight gain, antipsychotics can cause diabetes. Though the exact mechanism is currently unclear, it seems to be an effect of treatment that is independent of weight gain.

The rate of onset of diabetes in patients on antipsychotics is double the expected rate for the population at large. The insulin resistance these drugs cause has also been linked to a range of problems, such as polycystic ovaries.

Epilepsy

All antipsychotics may trigger seizures in susceptible individuals. This ranges from rare with haloperidol to more common with clozapine.

Hormonal changes

All antipsychotics, except clozapine and quetiapine, increase the level of the hormone prolactin. This may cause lactation (the production of breast milk) and an increase in breast size. To a lesser degree, men may experience similar effects.

There may be disruption or loss of menstrual cycle. This may give a false impression of being infertile, however, unprotected sex in these circumstances can still lead to pregnancy.

Lack of interest

Antipsychotics produce a state of indifference, and the problem is that long-term use or too high a dose may leave an individual apathetic, demotivated and indifferent to everything. Studies also suggest that they may be less likely to get married or involved in significant relationships, to find themselves jobs, or to get on with their lives compared with people who have the same illness, but who do not take continuous antipsychotics.

Metabolic syndrome

A combination of weight gain, raised lipid levels and high blood sugar is commonly referred to as metabolic syndrome, and is thought to increase the risk of later cardiovascular complications. For this reason, regular general health checks are now seen as important for anyone on an antipsychotic.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a state where individuals, usually shortly after starting treatment, become stiff, feverish and out of touch. In severe cases, the condition may be fatal if not detected quickly. NMS is closely related to catatonia.

Treatment may include:

  • Discontinuing all drugs
  • A muscle relaxant such as lorazepam
  • Electroconvulsive therapy (ECT) produces rapid responses in most cases

Other dopamine-related side effects

There are many aspects of parkinsonism that are still poorly understood and often unrecognized. One of these is that Parkinson’s disease is sometimes accompanied by painful sensory symptoms. Other features include a change in the oiliness of the skin or hair.

Similar changes may also occur with antipsychotics. The risk is that complaints of this type will be dismissed as impossible. The general effect of all these changes is to produce a great deal of what is now seen as a “schizophrenic look”. There may also be subtle changes in smell that can have real interpersonal effects.

Sedation

Antipsychotics are generally regarded as having a sedative effect, which may result in drowsiness and interfere with activities such as driving.

This sedation can sometimes be useful in helping sleep, but the drugs can also have the opposite effect. When taken in low doses in the evening, an antipsychotic can sometimes interfere with sleep. Even when taken in higher doses at night, antipsychotics may sedate, but yet give a very unsatisfying sleep. A common report from people who stop these drugs is that they sleep more soundly when not taking them.

These effects vary from person to person and from drug to drug.

Sexual side effects

Sexual side effects of antipsychotics can affect both men and women. They can include:

  • Loss of libido (sex drive)
  • Erectile dysfunction
  • Involuntary and sustained erections (priapism)
  • Involuntary ejaculation
  • Delayed or blocked orgasm
  • A change in the quality of orgasms

Note that priapism requires urgent medical attention.

Skin problems

Antipsychotics can cause skin problems such as:

  • Rashes, from an allergic reaction to the medication. This usually clears up in 24–48 hours after the drug is stopped.
  • Photosensitivity, which can make you more likely to burn when exposed to sunlight for any length of time. This is perhaps most common with chlorpromazine.

Stiffness/lack of movement

Impairment of movement (akinesia) is the central feature of Parkinson’s disease. When caused by antipsychotics in a mild form, it is felt as a slowing of spontaneous movements – this may not be unpleasant. In a more severe form, the feeling may be one of being restricted, even strait-jacketed, which can be distressing.

Antipsychotics slow all movements including facial expressions, and can result in:

  • Clumsiness
  • Noticeable delays in responding during a conversation
  • Drooling, due to the muscles of the face and mouth reacting slower to the build up of saliva
  • Leaning forward or to one side when walking
  • Difficulty in starting to walk, or once having started, finding it difficult to stop

Suicide

Antipsychotics can cause suicidal thoughts and feelings, even in healthy volunteers.

In clinical trials submitted to regulators, olanzapine and risperidone have been linked to more completed suicides than other drugs.

It is often said that suicide happens in patients with schizophrenia or psychoses because of concern over a future devastated by illness. While this might be right in some cases, it is almost certainly wrong in most cases. Suicide was rare in schizophrenia before chlorpromazine – the first antipsychotic – which suggests that many people are reacting adversely to the treatment they are put on. Another factor pointing to the drug is that the suicide rate during the first year of treatment is much higher than at any other time.

There may be a host of factors linked to suicide such as patients ending up in isolated circumstances, or abusing alcohol or street drugs, but medication is the one thing that both patients and their doctors can easily change.

Sympathetic system effects

The effects of antipsychotics on the sympathetic nervous system can produce symptoms such as:

  • Constipation
  • Difficulty urinating – this can affect both men and women
  • Erectile dysfunction
  • Low blood pressure, which may increase the risk of fainting and falls
  • Palpitations

Tardive dyskinesia

Tardive dyskinesia refers to a set of abnormal movements of the face and mouth. This may only appear several months after the drug has been started, or after it has been stopped – the term “tardive” means late or delayed. It involves lip-smacking, protrusion of the tongue and chewing movements, and it may extend to writhing movements of the body and limbs.

Tardive dyskinesia lasts for years after the drug has been discontinued. There is currently no cure.

Anything between 5% and 20% of people who take antipsychotics long-term and in high doses may be affected. But the problem can also happen after relatively low doses given for weeks rather than years.

Thirst

Up to 20% of individuals on long-term antipsychotics drink excessive volumes of water, high-calorie soft drinks, or tea and coffee. It is not clear whether this is caused by the dry mouth that some antipsychotics can induce, or whether the drugs also cause repetitive drinking apart from this.

Weight gain

Weight gain is the most common side effect of antipsychotics at standard doses. It may be linked to a number of factors including:

  • Changes to hormones and metabolism
  • Increased appetite
  • Increase in thirst, resulting in the consumption of high-calorie drinks
  • Reduced activity

Dieting alone is rarely successful in these cases, and the failure to lose weight may lead to frustration and guilt if it is not realized that the drugs are responsible.

Withdrawal

Withdrawal side effects can include a wide range of neurological problems and other disturbances. Any of the problems mentioned above can appear during withdrawal, including abnormal movements, muscle problems resulting in pain or spasms, akathisia, irritability, aggression, suicidal thoughts and feelings, or tardive dyskinesia. There may be stress intolerance, appetite problems, pain all over the body even on brushing one’s hair, and mood swings that might seem like depression to others.

For some people, withdrawal may be impossible.

Further reading