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What Are the Side Effects of Antipsychotic Medications?

What Are the Side Effects of Antipsychotic Medications?


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Antipsychotic medications are mainly used to treat certain mental health conditions or symptoms of psychosis, like hallucinations or delusions.

Like most other medications, antipsychotic drugs may have certain side effects. These can range from hardly noticeable to severe.

The type and severity of side effects you get may depend on the type of medication and how often you take it.

It’s natural to feel overwhelmed or concerned if you’re just starting out on this type of medication or are exploring your treatment options. The good news is that these medications are effective at managing many symptoms.

For example, if you’re experiencing hallucinations, these could go away after just a few days of taking your meds. Some other symptoms, such as delusions, may take up to 6 weeks to be managed.

Everyone responds a little differently to antipsychotic medication.

It’s highly advisable that you take these medications under a professional’s supervision and that you always let them know about side effects you may be experiencing.

It’s not unusual for someone to try different types of antipsychotic medications or dosages before they find a combination that works.

This “trial period” might feel discouraging, but it’s part of a process that may lead you to feel better in the long term.

Antipsychotic medications are mainly used to treat the symptoms of psychosis, although they can help manage symptoms of other mental health conditions.

You might also take antipsychotic medication alone or in combination with other medications if you have a mental health condition or a neurological disorder such as:

  • schizophrenia
  • bipolar disorder
  • delirium
  • post-traumatic stress disorder
  • obsessive-compulsive disorder
  • generalized anxiety disorder
  • an eating disorder
  • ADHD
  • Parkinson’s disease
  • severe depression (known as psychotic depression)
  • chronic depression without psychosis

Antipsychotic medications won’t cure a condition but rather help you manage the symptoms you’re experiencing. Oftentimes, you may be on an antipsychotic for months or years.

It’s important that you not stop taking your medication (even if you’re feeling well) without talking with your health professional first.

In most cases, these medications need to be gradually tapered down in dosage to avoid further side effects. This means they have to be gradually decreased in dosage so your body can make the adjustment.

There are two main types of antipsychotics: typical and atypical.

Older medications, or first-generation medications, are called “typical” antipsychotics or neuroleptics. They include:

  • haloperidol
  • chlorpromazine
  • fluphenazine
  • perphenazine

The newer medications, or second-generation antipsychotic medications, are known as “atypical” antipsychotics. Some examples are:

  • risperidone
  • olanzapine
  • aripiprazole
  • lurasidone
  • paliperidone

All prescription medications can have side effects, and antipsychotic drugs are no exception.

Every body is different, so not everyone experiences the same side effects or with the same intensity. You might find you don’t notice any side effects at all, depending on the medication and your unique situation.

If you experience side effects, these can decrease after a few weeks of taking the drug. If this doesn’t happen, you might want to talk with your doctor about the possibility of changing the brand or the dosage.

It’s important that you don’t suspend the medication without consulting with your healthcare team first.

Antipsychotic medications can have both physical and psychosocial effects, and some of them can be long-term.

Physical side effects

  • Dizziness or blurry vision.
  • Drowsiness. You may feel sleepy, especially when first starting the medication, so don’t drive until you know how the medication affects you.
  • Sexual challenges. These can be related to the increase in the hormone prolactin. It can cause you to have a lower sex drive. If you have a penis, you might have difficulty getting an erection or have ejaculation problems. If you menstruate, you could notice your cycle becoming irregular.
  • Weight gain. This is often a side effect of atypical antipsychotic medications.
  • Digestive issues. You might feel nauseous, have a dry mouth, or have constipation or vomiting.
  • Low blood pressure.

Psychosocial side effects

  • Restlessness. You may experience agitation or episodes of high anxiety.
  • Mental fog. You might have a hard time thinking clearly or focusing on a task. You might also have difficulty recalling information.
  • Loss of motivation. You might feel like you lack the drive to accomplish tasks or feel like you’re not interested in the things you used to do.
  • Social withdrawal. You could feel inclined to stay home more often or avoid certain social situations.

Long-term effects

  • Uncontrollable movements. A side effect of some antipsychotic drugs is a condition known as tardive dyskinesia. It causes tics and tremors, oftentimes around your mouth. You can’t control these movements, and sometimes it doesn’t go away by stopping the medication. Usually, this is a side effect of typical antipsychotics.
  • Type 2 diabetes. Your chance of developing type 2 diabetes depends on the type of antipsychotic medication you take. Since weight gain is a side effect of some antipsychotic medications, you might develop a slightly increased risk for diabetes.
  • Metabolic syndrome. This includes a cluster of symptoms and conditions such as high blood pressure, heart disease, high cholesterol, and diabetes.

Not everyone experiences these side effects, and if you do, these can often go away after a while or after changing dosage or the type of drug.

There are some things you can do to manage some of the side effects you may experience. Talking with your healthcare team is highly advisable and can help you reduce unwanted effects.

  • Taking other medications. Some drugs can counteract some of the possible side effects. For instance, if you have weight gain as a result of your antipsychotic medication, you may be given a drug such as metformin to manage your weight gain or risk for diabetes.
  • Developing or reinforcing healthy habits. A few lifestyle habits can help you reduce the effects of medication. For example, getting 8 hours of sleep every day, eating fresh vegetables and fruits, and exercising a few times per week.
  • Seeking support. Talking with a psychotherapist or joining a support group may help you manage the psychosocial side effects of antipsychotic medications.

When someone abruptly stops taking their antipsychotic medication, they could experience a few unwanted effects.

Some people might also experience a relapse in symptoms if their medication is stopped. In some cases, these symptoms can be worse than before taking the drug.

Stopping your medications all of a sudden can cause what’s called “rebound psychosis,” which means your psychosis symptoms may come back as soon as you stop your drug.

Even if you go off your medications under the supervision of your healthcare team, you might see your symptoms coming back within 3 to 6 months.

It’s advisable that you discuss these instances with a health professional and make a treatment plan that covers all your bases.

Since antipsychotic medications come in a variety of forms, a healthcare professional can guide you towards the options that may work better for you.

Some questions you might consider are:

  • What forms does my medication come in? Does it come in pills, capsules, liquids, injections, patches, or tablets dissolved under the tongue?
  • What are the most common side effects, and how long do they last?
  • Will I have to take additional medications if I experience side effects?
  • What happens if I miss a dose?
  • What happens if I stop taking the medication?
  • Will I be taking this medication forever?
  • Are there any foods, drinks, supplements, or drugs I should be careful with when taking this drug?

Some antipsychotic medications may cause you to experience side effects. These can often go away after a few weeks, or they may be long term.

Because antipsychotic drugs can help you manage symptoms of psychosis, and may make you feel better overall, it’s advisable that you weigh the challenges versus the benefits. Discussing this with a healthcare professional can help you make the right decisions for your situation.


What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication

Background: Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure.

Method: An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact.

Results: MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important.

Conclusions: MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Keywords: Medication side effects PROM participatory methods schizophrenia self report.


Every antipsychotic has its own possible side effects. Not everyone who takes antipsychotics will experience side effects, but many people do.

This page lists the most serious side effects that are possible with any antipsychotic drug. Some of these side effects are rare.

Certain types of antipsychotic may also have other side effects which aren&rsquot listed here. The British National Formulary (BNF) has an A-Z list of drugs licensed for use in the UK. This list has links to find out more information about each drug, including information about side effects.

See our page on coping with side effects for guidance on what to do if you experience one of these side effects.

Antimuscarinic effects

Antimuscarinic effects are side effects caused by changes to the level of the chemical acetylcholine in your body. These effects are sometimes called anticholinergic effects.

If your level of acetylcholine changes, this can have effects all over your body. These effects include:

  • blurred vision
  • confusion and agitation
  • constipation, which may become life-threatening if not treated
  • difficulty urinating
  • drowsiness
  • dry mouth, which can cause tooth decay in the long term
  • erectile dysfunction
  • hallucinations
  • hot or dry skin, and decreased sweating
  • increased pressure in the eye
  • low blood pressure (taking hot baths increases this risk)
  • nausea (feeling sick)
  • rapid heartbeat and disturbed heart rhythm.

Antimuscarinic effects are more common with some antipsychotics than others. In particular, clozapine may be more likely to cause severe constipation than other types of antipsychotic.

These effects can also happen with other types of medication, such as tricyclic antidepressants and anti-Parkinson's drugs.

"With haloperidol my tongue hung out of my mouth and my lips were stretched wide and open. Quietiapine made me feel stoned initially, with huge weight gain."

Bed-wetting

Bed-wetting can be a side effect of antipsychotics. It is more common with some antipsychotics than others.

Blood disorders

Certain blood disorders can be a side effect of antipsychotics. These include:

Agranulocytosis

Agranulocytosis is a blood disorder which involves the loss of one type of white blood cell. It means that you are more likely to catch infections and less able to fight them. It is very serious and people have been known to die from it.

If you have the following symptoms, it may be a sign that your immune system is not working as well as it should:

If you experience these symptoms, you should contact your doctor straight away.

The risk of agranulocytosis is higher with clozapine than with other antipsychotics. If you take clozapine, you will have your blood tested regularly to check for this.

Blood clotting disorders (venous thromboembolism or VTE)

These include deep vein thrombosis (DVT) and pulmonary thrombosis (blood clot in the lung), which can be life-threatening.

Reduced white blood cells

Taking antipsychotics may cause a reduction in your white blood cells.

Body temperature problems

Antipsychotics can cause problems with regulating your body temperature. It may become too high or too low, both of which can make you feel unwell.

Emotional effects

Antipsychotics can sometimes make you feel:

  • anxious
  • excitable
  • agitated
  • aggressive
  • depressed (although some antipsychotics may have an antidepressant effect, making you feel less depressed)
  • restless and unable to keep still
  • out of touch with reality
  • socially withdrawn and detached from those around you.

Eye problems

Certain antipsychotics may cause various eye problems. These include:

  • blurred vision and difficulty reading
  • a build-up of granular deposits in the cornea and lens. This doesn&rsquot usually affect your vision
  • degeneration of the retina, which is the light-sensitive part of the eye. This can affect your vision
  • glaucoma, which is a serious eye condition
  • oculogyric crisis, which affects the muscles that control your eye movements. It can cause your eyes to turn suddenly, so you can&rsquot control where you look.

All antipsychotics also have the potential to cause narrow-angle glaucoma. This is a medical emergency. If you've ever had glaucoma or eye problems, you should be very cautious about taking antipsychotic drugs. You may want to avoid certain antipsychotics completely, especially those with antimuscarinic effects.

If you&rsquore concerned about this, you can speak to your doctor or psychiatrist to find out more.

Heart problems

Antipsychotics may cause certain heart problems, such as:

  • increased heart rate
  • heart palpitations, which are heartbeats that suddenly become more noticeable in your chest
  • effects on your heart rhythm. This has been known to cause sudden death in extreme cases. The risk of this is especially linked to being on a high dose, or taking more than one antipsychotic at the same time.

See our pages on taking antipsychotics safely and dosage of antipsychotics for more information on the risks of heart problems with antipsychotics. This includes information on how you can manage these risks.

Liver disorders

Certain antipsychotics may cause liver disorders and jaundice (yellow skin).

Metabolic syndrome

Metabolic syndrome is the medical name for a combination of the following symptoms:

  • weight gain and obesity
  • high blood sugar
  • diabetes
  • high blood pressure
  • high cholesterol.

You don&rsquot have to experience all of these symptoms to be diagnosed with metabolic syndrome.

Taking antipsychotics can increase your risk of developing metabolic syndrome. If you experiencing metabolic syndrome, this means you are at higher risk of developing:

This risk of this is increased even more if you have an unhealthy lifestyle. Your doctors may suggest trying to eat a healthier diet and get enough physical activity can help to reduce this risk.

See our pages on food and mood for healthy eating tips, and physical activity and your mental health for lots of ways to get more active. If you have a difficult relationship with food and eating, our pages on eating problems may help.

You will also need to have regular health checks before and during your treatment. See our page on taking antipsychotics safely for more information.

Neuroleptic malignant syndrome (NMS)

NMS is a rare but serious neurological disorder, which means it affects your nervous system.

It can happen as a side effect of taking antipsychotics. It may also occur as a withdrawal symptom if you stop taking antipsychotics. If it does occur, it usually develops rapidly over 24 to 72 hours.

  • sweating or fever, with a high temperature
  • tremor (shaking), rigidity (feeling stiff and unable to move your muscles) or loss of movement
  • difficulty speaking and swallowing
  • rapid heartbeat, very rapid breathing and changes in blood pressure
  • changes in consciousness, including confusion and lethargy, stupor or coma.

High temperature and rigidity are usually the first symptoms to appear. This means NMS can sometimes be confused with an infection. But NMS can be very dangerous if it&rsquos not detected and treated. In rare cases, it can be fatal.

If you&rsquore worried that you may have symptoms of NMS, you should contact your GP urgently or call 999 for an ambulance.

What's the treatment for NMS?

If you experience NMS, the treatment is most likely to involve admitting you to hospital, stopping your antipsychotic medication and reducing your fever.

Some other methods of treatment are used, although the evidence for the use of these is not as strong. These methods may include using:

  • medication to relax your muscles
  • medication to counter the chemical effects that are thought to cause NMS .

The symptoms may last for days, or even weeks, after coming off the antipsychotic that's causing them. Many people who have had NMS once go on to get it again.

If you experience NMS, you should only take antipsychotics afterwards if they are essential for your mental health. And you should have the lowest dosage possible that still gives the positive effects.

Neuromuscular side effects

Antipsychotics interfere with the brain chemical dopamine, which is important in controlling movement. Antipsychotics may therefore cause movement disorders. These are most common with first generation (older) antipsychotics and less likely with the newer antipsychotics. They include the following:

Parkinsonism

Some neuromuscular side effects are similar to the effects of Parkinson&rsquos disease, which is caused by the loss of dopamine. These effects are known as Parkinsonism, and they include the following:

  • Your muscles become stiff and weak.
  • You find it more difficult to make facial expressions.
  • Certain small movements feel difficult, such as writing or picking up objects with your hands.
  • You develop a slow tremor (shaking), especially in your hands.
  • Your fingers move as if you are rolling a small object between them.
  • When walking, you lean forward, take small steps and find it difficult to start and stop.
  • Your mouth hangs open, and you dribble.

Loss of movement

You may find it difficult to move and your muscles may feel very weak.

Having little energy to move is also a symptom of depression, so if you experience this your doctor or psychiatrist may ask if you&rsquore feeling depressed.

Akathisia (restlessness)

Akathisia is a feeling of restlessness that can affect your body and your emotions. For example, you might:

  • feel intensely restless and unable to sit still
  • rock from foot to foot, shuffle your legs, cross or swing your legs repeatedly, or continuously pace up and down
  • feel emotionally tense and uneasy.

Doctors might confuse these symptoms and think you are anxious or agitated. If they don't know that you have akathisia, they may suggest taking a higher dose of your antipsychotics, to help you feel calmer.

But if you have akathisia, increasing your dose of antipsychotics won&rsquot help. So if you are diagnosed with akathisia, your doctor or psychiatrist may suggest taking another medication to reduce its effects, as well as your antipsychotic.

Muscle spasms

Muscle spasms are when a muscle in your body contracts against your control, and you cannot relax the muscle. They can be painful and may have serious effects. For example:

  • If a spasm affects the muscles of your larynx (voicebox), you may have problems with your voice. This is called dysphonia. You might find it difficult to speak normally, and people may find it hard to understand you.
  • If a spasm affects the muscles that control your eye movements, it can makes your eyes turn suddenly. It may mean you can&rsquot control where you look. This is called an oculogyric crisis. This can feel very unpleasant. It could also be dangerous, for example if it happens while you are crossing the road or pouring boiling water from a kettle.

"I experienced twitching, stumbling and slurred speech."

Sedation (sleepiness)

Sedation, or sleepiness, is a common side effect of many antipsychotics. It is more common with certain antipsychotics than others, such as chlorpromazine and olanzapine.

Sedation can happen during the day as well as at night. So if you experience this you might find it very hard to get up in the morning. Or it might feel difficult to motivate yourself to be active during the day.

"Antipsychotics knock me out and make it very hard to function normally."

Seizures (fits)

Many antipsychotics have the potential to cause fits. If you've ever had fits in the past, you should be particularly cautious about taking antipsychotic drugs.

Sexual and hormonal problems

Sexual problems are a possible side effect of certain antipsychotics. The symptoms vary for different people, and may include:

  • acne (a condition causing spots and oily skin)
  • increased hair growth across the face and body
  • osteoporosis (a disease where your bones become weaker and more likely to break)
  • reduced sexual desire, difficulty getting aroused and inability to orgasm
  • breast development and the production of breast milk. This can affect anyone, including if you were assigned male at birth.

If you have a penis, you may experience spontaneous ejaculation or priapism (a painful erection that lasts for several hours). If you experience priapism, it requires urgent medical attention. Contact your GP for an urgent appointment or go to Accident & Emergency (A&E).

If you have a vagina, you may experience vaginal dryness. And if you would normally have periods, they might stop or become irregular. But these changes can be unpredictable. Your periods may return, so you could still get pregnant if you have unprotected sex.

Some second generation antipsychotics may be less likely to cause these sexual side effects. You can speak to your doctor, psychiatrist or pharmacist if you are concerned about these effects.

"Amisulpride has made my breasts grow and lactate. After having blood tests, it turns out that my prolactin levels have sky-rocketed, which is why I experienced those side effects. I am also now at risk of osteoporosis in the future."

Skin problems

Antipsychotics can cause various skin problems, for example:

  • Allergic rashes. These usually occur within the first two months of starting treatment. They usually disappear when you stop taking the drug. If you get a rash, you should contact your GP straight away to have it checked.
  • Increased sensitivity to sunlight, especially at high doses. If you're taking antipsychotics, you may need to take extra care to protect yourself from the sun.
  • A blue-grey discolouration in some skin types.

Suicidal feelings or behaviour

Some people experience suicidal thoughts and behaviours while taking antipsychotics. This can happen particularly in the early stages of taking this medication.

If you are concerned about experiencing suicidal feelings while taking antipsychotics, speak to your doctor or psychiatrist.

If you feel unable to keep yourself safe, it's a mental health emergency.

Tardive dyskinesia (TD)

Tardive dyskinesia (TD) is a side effect of certain medications, mainly antipsychotics. It involves experiencing sudden, jerky or slow twisting movements in your face or body.

See our pages on tardive dyskinesia to find out more. This includes information on what TD is, what treatments and support are available, and ways to help yourself cope.

Tardive psychosis

Tardive psychosis is a term used to describe new psychotic symptoms that begin after you have been taking antipsychotics for a while. Some scientists believe that these symptoms may be caused by your medication, not your original illness returning. The word 'tardive' means that it's a delayed effect of the medication.

This risk of tardive psychosis is one reason why it&rsquos a good idea to withdraw slowly from your medication, if you decide to stop taking it. This is especially important if you have been taking it for a long time, as withdrawing slowly gives your brain time to readjust.

Weight gain

Weight gain is a very common side effect of many antipsychotics, particularly some of the second generation (newer) drugs. This may be because antipsychotics increase your appetite, so you want to eat more than usual. They may also cause you to become less active, for example if they make you feel very tired.

If you put on a lot of weight, this can increase your risk of developing diabetes and other physical health problems. It's also understandable if you feel upset or frustrated about these changes to your body.

If you experience weight gain, your doctor or psychiatrist may suggest switching to another antipsychotic medication. They may also suggest that you try to eat a healthy diet and increase your level of physical activity.

See our pages on food and mood for healthy eating tips, and physical activity and your mental health for lots of ways to get more active. If you have a difficult relationship with food and eating, our pages on eating problems may help.


Living with antipsychotic medication side-effects: the experience of Australian mental health consumers

The present study explores people's experience of living with antipsychotic medication side-effects. Qualitative data were gathered through semistructured interviews with 10 mental health consumers in a community care setting in Australia. The interview transcriptions were content analysed, and enhanced by combining manifest and latent content. Important contextual cues were identified through replaying the audio-recordings. Several main themes emerged from the analysis, including the impact of side-effects, attitudes to the use of medication and side-effects, and coping strategies to manage medication side-effects. Each participant reported between six and seven side-effects on average, which were often pronounced and had a major disruptive impact on their lives. Of these effects, the most commonly mentioned was sedation, which the participants described as leaving them in a 'zombie'-like state. Most participants expressed an attitude of acceptance about the side-effects. The participants' most common strategy to manage side-effects was to change the dosage of the medication. Other common side-effect management strategies involved using other medications to control side-effects, and diverse self-help techniques, the most common of which was relaxation/distraction techniques.

Keywords: antipsychotic medication consumer interviews mental health qualitative research.


Results

Participants

All samples had similar demographic characteristics. (see Table 1). The median BPRS score of sample 2 was 45, which is close to the median score of 47.3 noted in individuals with established schizophrenia (McCleery et al. Reference Mccleery, Ventura, Kern, Subotnik, Gretchen-Doorly, Green, Hellemann and Nuechterlein 2014). Clinical state did not change significantly across the two time points (Web-Table S1 r = 0.85 p < 0.001 median scores: T1 45, T2 48 and 46% with 0 change).

Table 1. Demographic and clinical characteristics

Phase 1: Measure generation

The Delphi exercise identified items of: (i) uncertain validity, (ii) detected only by observation or (iii) duplication and these items were removed. Other items were clarified and additional ones related to newer antipsychotic medications added. Following these changes, the research team (including the service user researchers) reworded all questions into a simple, easy-to-read format.

Prompted by the list of side-effects and following a discussion of personal experiences, focus group participants removed a duplicate item, generated eleven new items and advised on presentation and scaling. The expert panel (n = 6) added one new item and a comments box and considered the questionnaire both comprehensive and the right length.

At this point, there were 54 items each with three ratings: intensity (0-not at all, 1-mild, 2-moderate, 3-severe), distress (yes or no) and life impact (4-point Likert scale). Two additional items noted the most important three side effects and the balance of benefits of taking medication.

Phase 2: Feasibility and draft items

In sample 2, the side effects reported most often (see Web-Table S2) were ‘feel tired’ (77%), ‘put weight on’ (70%), ‘passing urine’ (67%), ‘thirsty’ (67%) and ‘memory issues’ (65%) and very similar results were obtained in the replication group (sample 3 Web-Table S2). One low-frequency item was dropped as it had less value and was difficult to self-report leaving a 53-item scale to assess psychometric properties. MSE has a Flesch reading ease score of 103 where scores of 90–100 are regarded as ‘very easy’ to understand (Flesch, Reference Flesch 1948). MSE was acceptable to the vast majority of the sample (99% found it easy to understand, 93% easy to complete and 93% an appropriate length). Three service users disliked completing the measure and 20% found some questions distressing, which were those associated with sensitive intimate issues – sexual problems, enuresis and constipation. It takes about 15 min to complete.

Psychometric analyses

Descriptive data

The mean total number of side effects reported was 21 out of 53. Intensity, life impact and distress scores were skewed towards the lower end of the scale (see Web-Table S3). As expected a higher side-effect burden correlated with more distress and life impact and all these correlations were statistically significant (see Web-Table S4). As anticipated, neither age nor gender (Web-Table S5) affected side-effect endorsement (p > 0.1 in all cases) and all these results were replicated in sample 3 (Web-Tables S6 and S7).

Reliability

Cronbach's alpha for the total side-effects score was 0.96, indicating very high correlations between items. At the item level, the weighted Kappa coefficient indicated at least fair agreement for intensity items. Non-significant coefficients emerged only for ‘fits’, ‘rash’ and ‘catatonia’ side effects, probably due to their low frequency (see Web Table S6). At the subscale level, all scores were highly correlated (0.81–0.96) between the two time points and there were no statistically significant differences in the mean scores, indicating the instrument's good test–retest reliability (see Web Table S2). Symptoms did not affect reliability as it was stable for both high and low BPRS scorers [high scorers (above the median – 45): ρ = 0.85, p < 0.001 low scorers (below median): ρ = 0.94, p < 0.001].

Validity assessment

(i) We established concurrent convergent validity by comparing the side-effects summary scores with clinical state measures (sample 2). As expected, a greater number of side effects were related to poorer measures of general mental health (GHQ, SF-36 mental component) and physical health (SF-36) as items overlap (see Table 2).

But our specific psychosis mental state measure did not have overlapping items so should not be related. We investigated side-effect reporting in the low and high BPRS scorers and found evidence of discriminant validity as the two BPRS groups did not differ in side-effect reporting (total side effects mean 22.7 v. 19.3 Z = 0.86, p = 0.39 intensity median 43.1 v. 29.7 Z = −1.26, p = 0.21 distress median 29 v. 19 Z = −0.95, p = 0.35). However, high BPRS scorers, as expected, reported significantly higher life impact (median 9 v. 2 Z = −2.858, p = 0.004) given that higher symptom levels plus the side effects are likely to have the highest impact on everyday life.

(ii) We established concurrent convergent validity between GASS and MSE (sample 3 Table 3). At the similar item level, the agreement in endorsement varied from 70% to 90%. For distress agreement ranged from 73% to 100%. All weighted kappa coefficients were significant and indicated fair to substantial agreement. At the total score level (all items included in both scales), the MSE and GASS subscales were highly correlated (total side effects: r = 0.8, intensity: r = 0.8 and distress: r = 0.7, p < 0.001 in all cases).

Table 2. Correlation coefficients between the MSE scores and SF-36 and GHQ scores

Table 3. Similar Item level agreement assessed for items with at least 15 individuals reporting on the MSE

a Considered if the item was endorsed on both scales.

For concurrent criterion validity, we measured the effects of a side effect most often associated with Clozapine prescription, drooling. These results were replicated in sample 3 (N50), and those prescribed Clozapine (N30 60%) were more likely to report drooling and when they experienced drooling it was more intense compared with those prescribed other medications [(i) frequency of reporting 80% v. 35% χ 2 = 10.314, df = 1, p = 0.001 higher intensity when reported, median: 1.6 v. 0.7 Mann–Whitney U = 157.5, p = 0.003]. The pattern of results was the same for sample 2 although there were fewer people prescribed clozapine (N9 21%). We tested for differences in distress and life impact after merging the two samples but no statistically significant differences emerged (χ 2 = 0.570, df = 1, p = 0.450) or life impact (median: 1 in both cases Mann–Whitney U = 183.0, p = 0.130) suggesting that drooling is distressing and affects life, whichever drug produced the effects.

The most important side effects

The pattern of most important side effects was the same samples 2 and 3 with only one difference, drooling was chosen more often in sample 3 selecting this item (21% v. 11.6% χ 2 = 5.488, df = 1, p = 0.019) probably because it contained more people prescribed clozapine.

Participants (merged sample N93) endorsed 42 of our 53 items as one of the three most important side effects (see Web Table S8) providing further validity for the breadth of scale items. The three most often mentioned were feeling tired, drooling and putting on weight selected by 16–23% of the total sample. The remaining items were selected by <9% suggesting that what bothers an individual is idiosyncratic.

What determines an individual's choice of the most important side effect?

A participant's choice did not follow the endorsement frequency. For instance, 62% identified memory problems, but they were only mentioned as ‘most important’ by 16%. As many ‘most important’ items were low frequency, we concentrated on the side effects most frequently reported – feeling tired, drooling and putting on weight. Choosing tiredness or drooling was not related to how an individual rated its severity, distress or life impact. However, for ‘putting on weight’ those who mentioned it as most important also rated it as more severe (60% v. 29.4%, χ 2 = 6.384, df = 1, p = 0.041), having more life impact (70% v. 20.4%, χ 2 = 12.432, df = 1, p = 0.006) and being more distressing (90% v. 27.5%, χ 2 = 13.926, df = 1, p < 0.001).


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Maju Mathews, Dr. Maju Mathews is Assistant Professor of Psychiatry, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Sylvia Gratz, Dr. Gratz is Associate Professor of Psychiatry, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Babatunde Adetunji, Dr. Adetunji is Attending Psychiatrist, MHM Correctional Services, Philadelphia, Pennsylvania.

Vinu George, Dr. George is from Albert Einstein Medical Center, Philadelphia, Pennsylvania.

Manu Mathews, Dr. Manu Mathews is from the Cleveland Clinic, Cleveland, Ohio.

Biju Basil, Dr. Basil is from Drexel University College of Medicine, Philadelphia, Pennsylvania.


The Side Effects Of Common Psychiatric Drugs: Antipsychotics

(Called Major Tranquilizers or Neuroleptics)

Brand Names (Generic Names):

Older Antipsychotics

Mellaril (thioridazine hydrochloride)

Moban (molindone hydrochloride)

Prolixin (fluphenazine hydrochloride)

Repoise (butaperazine Maleate)

Serentil (mesoridazine besylate)

Newer Atypical Antipsychotics

Geodon (ziprasidone hydrochloride)

Symbyax (fluoxetine and olanzapine –antidepressant/antipsychotic mix)

Side Effects:

Abnormal gait (manner of walking)

Decreased sexual interest or ability

Difficulty breathing, swallowing or fast

Difficulty falling asleep or staying asleep

Difficulty urinating or loss of bladder control

Fast, irregular, or pounding

Hyperglycemia (abnormally high blood sugar)

Hypoglycemia (abnormally low blood sugar)

Jaw, neck, and back muscle spasms

Muscle or joint stiffness, pain, or weakness

Pain in arms, legs, back, or joints

Pain in the upper right part of the stomach

Painful erection that lasts for hours

Pancreatitis (inflammation of pancreas, a gland near the stomach that helps digestion)

Shaking hands that you cannot control

Swelling of the arms, hands, feet, ankles, or lower legs

Tachycardia (heart irregularity)

Yellowing of the skin or eyes86

GENERAL WARNINGS AND STUDIES ON ANTIPSYCHOTICS:

2001: The Journal of Toxicology reported that the newer antipsychotics “will soon account for the majority of poisonings from antipsychotic agents that get presented to health care facilities in the U.S.”90 Researchers found, “[T]he ingestion of a single tablet of clozapine (Clozaril), olanzapine (Zyprexa) and risperidone (Risperidal) may cause significant toxicity in a toddler. Ataxia (involuntary muscular movement), confusions, EPS (extrapyramidal symptoms – nerve damage), coma and respiratory arrest have been reported following ingestion of 50-200 mg of clozapine in toddlers.”91

September 2003: The FDA requested the makers of six newer antipsychotic drugs add a caution to their labeling language about the potential risk of diabetes and blood sugar abnormalities.92

June 2004: The Australian Therapeutic Goods Administration published an Adverse Drug Reactions Bulletin reporting that the newer antipsychotics could increase the risk of diabetes.93

September 22, 2005: Dr. Jeffrey Lieberman of Columbia University and other researchers published a study in The New England Journal of Medicine that compared the older generation of antipsychotics with several newer ones. Far from proving effectiveness, of the 1,493 patients who participated, 74% discontinued taking antipsychotic drugs before the end of their treatment due to inefficacy, intolerable side effects or other reasons. After 18 months of taking Zyprexa, 64% of the patients stopped taking it—most commonly because it caused sleepiness, weight gain or neurological symptoms like stiffness and tremors.94

December 1, 2005: Researchers found that 18% of nearly 23,000 elderly patients taking the older antipsychotics died within the first six months of taking them.95

May 2, 2006: USA Today released the results of an analysis of FDA data that showed at least 45 children died between 2000 and 2004 from the side effects of antipsychotic drugs (Clozaril, Risperdal, Zyprexa, Seroquel, Abilify and Geodon). Despite an adults-only FDA approval for these drugs, according to USA Today, up to 2.5 million children were prescribed them. As the FDA’s Adverse Drug Reactions reporting database only collects 1% to 10% of drug-induced side effects and reported deaths, the true child death rate could be between 450 and several thousand. Further, there were 1,328 reports of other side effects, some life-threatening, such as convulsions and low white blood cell count.96

January 5, 2008: The Lancet (Britain) published a study where the authors concluded “that the routine prescription of antipsychotic drugs early in the management of aggressive challenging behavior, even in low doses, should no longer be regarded as a satisfactory form of care.”97

April 2008: The American Geriatrics Society published a study entitled, “Antipsychotic Drug Use and Risk of Pneumonia in Elderly People,” which reviewed 22,944 elderly people with at least one antipsychotic prescription. The results of the study showed that “antipsychotics were associated with an almost 60% increase in the risk of pneumonia…” concluding that elderly people are at greater risk of pneumonia, especially during the first week of antipsychotic drug treatment.98

April 9, 2008: Pharmacoepidemiology and Drug Safety published a study entitled, “The use of central nervous system [CNS] drugs and analgesics [painkillers] among very old people with and without dementia.” The study compared the use of CNS drugs in people aged 85 years or older, with and without dementia and concluded: “[T]he use of antipsychotics in people with dementia should arouse particular concern, because of the high risk of severe adverse events and the limited evidence of positive effects.”99

May 26, 2008: The Archives of Internal Medicine published a study about “Antipsychotic

Therapy and Short-term Serious Events in Older Adults With Dementia” that found:

“Serious events…are frequent following the short-term use of antipsychotic drugs in

older adults with dementia. Antipsychotic drugs should be used with caution even when

short-term therapy is being prescribed.”100

June 2008: The FDA issued a warning to healthcare professionals that conventional and

atypical antipsychotics are associated with an increased risk of mortality in elderly patients

treated for dementia-related psychosis. It specified that antipsychotics are not indicated

for the treatment of this condition. Additionally, the FDA required the manufacturers of

these drugs to add a boxed warning about this risk to the prescribing information. Older,

conventional antipsychotics were also to carry a “black box” warning about an increased

risk of death in some elderly people.101

April 2009: The Irish Medicines Board published in their Drug Safety Newsletter, a warning

about antipsychotics causing a risk of stroke and now increased risk of mortality in elderly

patients treated for dementia. This risk covers both typical and atypical antipsychotics.102

WARNINGS ON SPECIFIC ANTIPSYCHOTICS:

Abilify and other antipsychotic drugs have caused a potentially fatal condition called

neuroleptic malignant syndrome. Patients who develop this may have high fevers, muscle

rigidity, altered mental status, irregular pulse or blood pressure, rapid heart rate, excessive

sweating, and heart arrhythmias (irregularities).103

Body temperature regulation—disruption of the body’s ability to reduce core body

temperature—has been attributed to antipsychotic agents such as Abilify.104

April 2003: The U.S. consumer advocacy group Public Citizen conducted a review of

information published on Abilify, basing their evaluation primarily on publicly available

FDA reviews of information submitted by the manufacturer to gain FDA approval for

Abilify. Approval was based on five trials only lasting four to six weeks. According to

Public Citizen, “…nothing in these five trials can lead one to believe that aripiprazole

(Abilify) is a meaningful advancement in the treatment of schizophrenia.”105

The information insert on Abilify lists hyperglycemia (abnormally high blood sugar—

usually associated with diabetes), hypoglycemia (abnormally low blood sugar) and diabetes

as possible side effects.106

May 2008: Medsafe (New Zealand) posted a prescriber update called “Clozapine and

Achy Breaky Hearts” warning that clozapine can cause myocarditis [inflammation of the

heart muscle] that may be fatal. It was also associated with cardiomyopathy [disease of

the heart muscle]. While risk factors are unknown, pre-treatment cardiovascular screening

May 2008: Medsafe posted their June 2008 “Watching Briefs,” a report in which they

included a warning: “Use of clozapine in older patients carries a higher risk of adverse

reactions such as postural hypotension [low blood pressure], falls, sedation and constipation,

compared to use in younger patients. Therefore, increased clinical monitoring of the elderly

is necessary to ensure their safety.”108

September 17, 2007: The FDA issued an alert to Healthcare Professionals about

haloperidol (marketed as Haldol), stating: “Due to a number of case reports of sudden

death, TdP [Torsades de Pointes] and QT prolongation [TdP and QT prolongation are types

of heart abnormalities] in patients treated with haloperidol (especially when the drug is

given intravenously or at doses higher than recommended), the sponsor has updated the

labeling for haloperidol.” ECG (Electrocardiogram—a graphical recording of the cardiac

cycle produced by a special machine, a.k.a. EKG) monitoring was recommended if

haloperidol is given intravenously, even though haloperidol is not approved for intravenous

July 22, 2005: Eli Lilly & Co., the manufacturer of Zyprexa, agreed to pay $1.07 billion

to settle more than 8,000 claims against the drug, alleging it could potentially cause lifethreatening

September 22, 2005: Dr. Jeffrey Lieberman of Columbia University and other researchers

published a study in The New England Journal of Medicine comparing an older generation

of antipsychotics with several newer ones.111 After 18 months of taking Zyprexa, 64%

of the patients stopped taking it, most often because it was not well tolerated and caused

sleepiness, weight gain or neurological symptoms like stiffness and tremors.112

October 5, 2007: Eli Lilly issued an important Safety Information update on its website

and product labels for Zyprexa and Symbyax (combination of Zyprexa and fluoxetine, or

Prozac) warning of the risk of weight gain, hyperglycemia (increased blood sugar) and

hyperlipidemia (elevated fats in the blood and cholesterol).113

2008: The current Zyprexa Safety Information includes a “black box” warning of increased

risk of death in elderly patients with dementia, as well as the following warnings: High

level of fats in the blood, weight gain, high blood sugar, strokes and “mini strokes” (in

elderly people with dementia), neuroleptic malignant syndrome, tardive dyskinesia, low

blood pressure, trouble with judgment, thinking, and reflexes, trouble swallowing, body

temperature problems…and “this is not a complete list….”114

*Akathisia: A, meaning “without” and kathisia, meaning “sitting,” an inability to keep still. Patients

pace about uncontrollably. The side effect has been linked to assaultive, violent behavior.87

*Neuroleptic malignant syndrome: A potentially fatal toxic reaction where patients break into

fevers and become confused, agitated and extremely rigid. An estimated 100,000 Americans have

died from it after taking the older antipsychotics.88

*Tardive Dyskinesia: Tardive, meaning “late” and dyskinesia meaning, “abnormal movement of

muscles.” Tardive Dyskinesia is a permanent impairment of the power of voluntary movement of

the lips, tongue, jaw, fingers, toes and other body parts.89

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29 Ritalin Drug Label, fda.gov.

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31 Dr. Candace B. Pert, Letter to the Editor, TIME Magazine, 20 Oct. 1997, p. 8.

32 “Worsening Depression and Suicidality in Patients Being Treated with Antidepressant Medication,” FDA Public Health Advisory, 22

33 Gardiner Harris, “Antidepressant Study Seen to Back Expert,” The New York Times, 20 Aug. 2004.

34 “Antidepressant aggression concern,” BBC News Online, 21 Sept. 2004.

35 “Suicidality in Children and Adolescents Being Treated With Antidepressant Medications,” FDA Public Health Advisory, 15 Oct. 2004.

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82 “Depression in Children and Young People,” National Institute for Health and Clinical Excellence, Sept. 2005, pp. 16, 18 and 28.

83 FDA, “Antidepressant Use in Children, Adolescents, and Adults,” www.fda.gov/CDER/Drug/antidepressants?default.html, updated

85 “Antidepressant drug use and risk of venous thromboembolism,” Pharmacotherapy, Vol. 28, No. 2, 28 Feb. 2008.

86 Physicians’ Desk Reference, http://www.pdrhealth.com “ABILIFY Rx Only (aripiprazole) Tablets,” Package Insert, revised Mar.

2004 “GENERIC NAME: Aripiprazole BRAND NAME: Abilify,” Internet URL: http://www.MedicineNet.com, Last Editorial

Review: 9/8/04 “Aripiprazole Brand Name: Abilify,” Internet URL: http://www.HealthyPlace.com, Ty C. Colbert, Rape of the Soul,

How the Chemical Imbalance Model of Modern Psychiatry has Failed its Patients, (Kevco Publishing, California, 2001), p. 106.

87 Robert Whitaker, Mad in America: Bad Science, Bad Medicine, and the Enduring Mistreatment of the Mentally Ill, (Perseus

Publishing, New York, 2002), pp. 182, 186.

88 Op. cit., Robert Whitaker, p. 208.

89 George Crane, “Tardive Dyskinesia in Patients Treated with Major Neuroleptics: A Review of the Literature,” American Journal of

Psychiatry, Vol. 124, Supplement, 1968, pp. 40-47.

90 Michael J. Burns, “The Pharmacology and Toxicology of Atypical Antipsychotic Agents,” Journal of Toxicology, 1 Jan. 2001.

92 “FDA: Antipsychotic Drugs, Diabetes Linked,” Associated Press Online, 18 Sept. 2003.

93 “Atypical antipsychotics and hyperglycaemia,” Australian Adverse Drug Reactions Bulletin, Vol. 23, No. 3, June 2004.

94 Jeffrey A. Lieberman, M.D., et al., “Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia,” The New England Journal of Medicine, Vol. 353, No. 12, 22 Sept. 2005.

95 Philip S. Wang, et al., “Risk of Death in Elderly Users of Conventional vs. Atypical Antipsychotic Medication,” The New England

Journal of Medicine, Vol. 353, No. 22, 1 Dec. 2005.

96 Marilyn Elias, “New antipsychotic drugs carry risks for children Side effects can lead to bigger health problems,” USA Today, 2

97 Peter Tyrer, et al., “Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with

intellectual disability: a randomized controlled trial,” The Lancet, Vol. 371, 5 Jan. 2008.

98 Wilma Knol, M.D., et al., “Antipsychotic Drug Use and Risk of Pneumonia in Elderly People,” The American Geriatrics Society, Vol.

56, No. 4, pp. 661-666, Apr. 2008.80

99 Hugo Lovheim, M.D., Stig Karlsoon, R.N., Ph.D., et al., “The use of central nervous system drugs and analgesics among very old

people with and without dementia,” Pharmacoepidemiology and Drug Safety, 9 Apr. 2008.

100 Paula A. Rochon, M.D., MPH, FRCPC, et al., “Antipsychotic Therapy and Short-term Serious Events in Older Adults With

Dementia,” The Archives of Internal Medicine, Vol. 168, No. 10, 26 May 2008.

101 “Information for Healthcare Professionals Antipsychotics,” FDA, June 2008 “US FDA expands antipsychotic drug warning,”

102 “Update on the safety of antipsychotic medicines – risk of stroke and increased risk of mortality in elderly patients treated for

dementia,” Drug Safety Newsletter, Iss. 30, Apr. 2009, p. 5.

103 MedicineNet.com, Last Editorial Review: 9/8/04.

104 “Abilify Information,” Pharma-Help.com.

105 “The New Anti-Psychotic Drug Aripiprazole (ABILIFY),” Public Citizen’s eLetter, Apr. 2003.

106 Op. cit., “ABILIFY Rx Only (aripiprazole) Tablets,”

107 “Clozapine and Achy Breaky Hearts,” MedSafe, May 2008.

108 Watching Briefs, MedSafe, June 2008.

109 “Information for Healthcare Professionals Haloperidol (marketed as Haldol, Haldol Decanoate and Haldol Lactate),” FDA ALERT,

110 Jeff Swiatek, “Uncertainty was Driver in Zyprexa Deal,” IndianapolisStar.com, 11 June 2005.

111 Op. cit., Jeffrey A. Lieberman, M.D., et al.

112 “Study: New drugs little better for schizophrenia,” St. Petersburg Times, 20 Sept. 2005.

113 “Important Safety Information about ZYPREXA® (olanzapine),” Eli Lilly and Company, 5 Oct. 2007 “Lilly Announces Updates

to the Zyprexa and Symbyax U.S. Labels,” PRNewswire, Bio-Medicine, 5 Oct. 2007.

114 ZYPREXA Safety Information, www.zyprexa.com.

115 Physicians’ Desk Reference, http://www.pdrhealth.com.

116 Tracey McVeigh, “Tranquilizers ‘more lethal than heroin,’” The Observer, 5 Nov. 2000.

117 Matt Clark, Mary Hager, “Valium Abuse: The Yellow Peril,” Newsweek, 24 Sept. 1979 Dr. Patrick Holford, “How to Quit

Tranquilizers,” www.patrickholdford.com, 2008.

119 Op. cit., Tracey McVeigh.

120 “Elderly On Long-Acting Anxiety, Insomnia Drugs Have More Car Crashes,” Doctor’s Guide citing Journal of American Medical

121 “Agression, Violence & Bezodiazapines,” Benzo.org.uk, citing British National Formulary, 2001.

122 Benzo.org.uk, citing Professor C. Heather Ashton, Benzodiazepines: How They Work and How To Withdraw, Feb. 2001.

123 “The Influence on the Pharmaceutical Industry,” House of Commons, UK, Health Committee, Vol. 1, Mar. 2005. p. 65.

124 Tarja-Brita R. Wahlin, et al., “Falls and fall risk among nursing home residents,” The Journal of Clinical Nursing, Vol. 17, pp. 126-

125 “Europe-wide review recommends updates to product information for varenicline (brand name Champix),” MHRA, 14 Dec. 2008.

126 “Early Communication About an Ongoing Safety Review Varenicline (marketed as Chantix),” FDA, 20 Nov. 2007.

127 “Varenicline (marketed as Chantix) Information,” FDA Alert, 1 Feb. 2008.

128 Op. cit., House of Commons, UK, Health Committee, p. 65.

129 Anna Maria Dademan, “Flunitrazepam and violence—psychiatric and legal issues,” Department of Clinical Neuroscience,

Occupational Therapy and Elderly Care, Research Division of Forensic Psychiatry, Karolinska Institute, Sweden, 2000, p. 43.

130 “Zolpidem (‘Stilnox’) – Updated information – February 2008,” Theraputic Goods Administration, 21 Feb. 2008 “Club Drugs: An

Update,” Drug Intelligence Brief, Drug Enforcement Administration, Sept. 2001.

131 “FDA Safety Changes: Ambien, Primazin IM/IV, Hepsera,” Medscape, 28 Aug. 2008.

132 Peter Breggin, Toxic Psychiatry, (St. Martin’s Press, New York, 1991) p. 245.

133 Jerrold F. Rosenbaum, et al., “Emergence of Hostility During Alprazolam Treatment in Borderline Personality Disorder,” The

American Journal of Psychiatry, Vol. 141, No. 6 (June 1984), pp. 792-793.

134 David L. Gardner and Rex W. Cowdrey, “Alprazolam-Induced Dyscontrol in Borderline Personality Disorder,” The American

Journal of Psychiatry, Vol. 142, No. 1 (Jan. 1985), pp. 98-100.

135 “Xanax addiction extremely tough to kick,” MSNBC News Online, 2001.

136 Statement by Joseph A. Califano, Jr., Chairman and President, “Under the Counter: The Diversion and Abuse of Controlled

Prescription Drugs in the U.S.” The National Center on Addiction and Substance Abuse at Columbia University, July 2005.

137 Physicians’ Desk Reference, (Medical Economics Company, New Jersey, 1998), pp. 2822-2823 David L. Richman, M.D., Leonard

Roy Frank, and Art Mandler, Dr. Caligari’s Psychiatric Drugs (Alonzo Printing Co., Inc., California, 1984), p. 39.

138 Op. cit., David L. Richman, M.D., et al., pp. 38-39.

A previous article entitled Conventional Antipsychotics provides information. Conventional Antipsychotics, Loxitane ve Moban


Metabolic syndrome

It is well-known that antipsychotics often cause side effects, but there is less attention for the fact that these medicines can also cause type 2 diabetes, obesity and disrupted fat metabolism. These problems combined are also known as the metabolic syndrome.

Prof. dr. Jim van Os, Chair Division Neuroscience, Utrecht University Medical Centre. He is also Visiting Professor of Psychiatric Epidemiology at the Institute of Psychiatry in London. Jim works at the interface of ‘hard’ brain science, health services research, art and subjective experiences of people with ‘lived experience’ in mental healthcare.

Jim has been appearing on the Thomson-Reuter Web of Science list of ‘most influential scientific minds of our time’ since 2014. In 2014 he published his book ‘Beyond DSM-5‘, and in 2016 the book ‘Good Mental Health Care’.



Comments:

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  3. Abelard

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  4. Zolomuro

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