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Doctors Discuss Antipsychotic Side Effect

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Emma Yasinski
Emma Yasinski Staff Writer
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Antipsychotic side effects may include excessive gambling, impulsive behavior, and even suicidal ideation, according to several black box warnings the Food and Drug Administration (FDA) has slapped on the drugs over several years. Still, the drugs haven’t been removed from the market. That’s because they’re a crucial class of drugs despite the risks, as the psychosis they treat can be exceptionally dangerous. Here’s what you need to know.

What Are Antipsychotics?

Antipsychotic drugs are used to treat psychosis, a situation in which a person loses touch with reality. 

“Here in my room, I have a smoke detector,” says Maximilian Huhn, MD, a psychiatrist at The Technical University of Munich in Germany. “And I say, ‘OK, it’s a smoke detector.’ But a patient with a severe psychotic episode looks at the smoke detector and may not see a smoke detector, but a camera trying to observe them.”

Psychosis is most often associated with conditions such as schizophrenia and bipolar disorder. However, some people with other conditions such as Alzheimer’s disease can also experience psychosis.

Are Antipsychotics Used for Depression?

While antipsychotics were developed to treat psychosis, doctors sometimes prescribe them to help treat depression if typical antidepressants, such as SSRIs (selective serotonin reuptake inhibitors), alone haven’t alleviated symptoms. They might also prescribe them to help with insomnia or mood disorders in people with dementia. At the start of the pandemic, doctors started prescribing antipsychotics for people with dementia more frequently, and those prescriptions rates remained high throughout 2021.

Side Effects of Antipsychotics

There are two classes of antipsychotics. First generation antipsychotics block a neurotransmitter in your brain called dopamine. Second generation antipsychotics also block dopamine, but to a lesser extent than first generation drugs. The second generation antipsychotics also help raise levels of another neurotransmitter, serotonin, which can help you feel calm and content. That’s why they’re sometimes prescribed alongside antidepressants, which also often work by increasing availability of serotonin in your brain.

Huhn emphasizes that not all the effects of antipsychotics are well-understood. 

“The common mechanism that all psychotics have is that they block the dopamine receptor,” he said “That’s what they all do, more or less. They also bind to several other receptors, and this is why they have different side effects. But honestly, the problem is it’s not very well understood.”

First Generation Antipsychotics Include:

  • Chlorpromazine (Thorazine)
  • Fluphenazine (Prolixin)
  • Haloperidol (Haldol)
  • Mesoridazine besylate (Serentil)
  • Molindone (Moban)
  • Perphenazine (Trilafon)
  • Pimozide (Orap)
  • Thioridazine (Mellaril)
  • Trifluoperazine (Stelazine)

Second generation antipsychotics include:

  • Aripiprazole (Abilify)
  • Clozapine (Clozaril)
  • Lurasidone (Latuda)
  • Olanzapine (Zyprexa)
  • Paliperidone (Invega)
  • Metoclopramide (Reglan)
  • Risperidone (Risperdal)
  • Ziprasidone (Geodon)

Black Box Warnings

Both first and second generation antipsychotics come with an FDA “black box warning” the most serious warning of potential harm or death that the FDA publishes. The warning applies only to seniors with dementia because they have 1.6 – 1.7 times the risk of death than those not on antipsychotics. Most of the deaths linked to antipsychotic use are cardiovascular (heart failure, sudden death) or infections like pneumonia. It is not yet clear why the elderly are at higher risk of death or even if it’s the drug to blame or some other reason as yet undetected. 

Over the years, the FDA has also warned of dangerous skin reactions and impulsivity associated with the use of certain antipsychotics.

Though the antipsychotic side effect is rare, people who have been prescribed antipsychotics may experience impulsivity in different ways. It can manifest as a gambling addiction, inappropriate sexual behaviors or binge eating. 

When Jaymes, who has autism, was about 10 years old, a physician prescribed the antipsychotic aripiprazole, to help manage his irritability and outbursts. He began binge eating and over the course of a year, he gained 50 pounds. He also developed movement disorders in which he flailed his arms and scrunched his face, reported Spectrumnews.org.  

Another child in the Spectrum story dove into a deep depression after starting on the same antipsychotic. The problem, scientists told Spectrum News, is that while these side effects are rare, and generally disappear once you stop taking the drug, it’s impossible at this point to predict who will experience them.

Common  Antipsychotic Side Effect

Dopamine, the molecule that antipsychotics block, is important for many different brain functions, including helping you feel pleasure and motivation and initiating movement. More than 75% of people who are prescribed antipsychotic report experiencing side effects, according to a 2018 study of over 1,000 patients.

In that study, women were twice as likely to experience antipsychotic side effects as men were. Additionally, the higher the dose, or the more drugs a person had been prescribed, the more side effects they were likely to experience. As you might expect, people who say they experience more side effects also report lower quality of life.

Sandip Buch, MD, founder of Skypsyiatrist.com says, “The older antipsychotics are more tailored towards dopamine blocking. And that led to a lot of their side effects like extrapyramidal [movement-related] side effects, which is like feeling like you have to move a lot or tremor or shaking or Parkinson type of side effects.”

These are some of the most commonly reported side effects of antipsychotics:

  • Drowsiness/fatigue
  • Dry mouth
  • Difficulty enjoying sex
  • Weight gain
  • Movement disorders

Both mental health conditions such as schizophrenia and the antipsychotics used to treat them can make it difficult for your body to regulate its temperature. During extreme weather, this can be exceptionally dangerous. The Washington Post follows the footsteps of Stephan Goodwin, a young man with schizophrenia, who died after spending days in the sweltering Arizona heat in 2022.

Different Drugs Cause Different Antipsychotic Side Effect

Not every antipsychotic is effective for every patient, but all antipsychotics tend to be equally effective overall, says Huhn. The problem is that many patients choose to stop taking the medications due to the side effects. While the drugs all have similar levels of efficacy, their side effect profiles can vary greatly, he says. The most important part for a doctor determining a treatment plan for a patient with psychosis is discussing the different side effects with the patient and prioritizing the tolerability of the drug or drugs he or she prescribes. 

“The thing is that all antipsychotics work, that they are better compared to a placebo, but especially in the side effect profiles, they’re quite different,” he says, adding that “Especially with when you have had several episodes of schizophrenia, you should take medication for a long time—sometimes for your whole life. So it’s very important to have as few side effects as possible.”

But most of the drugs were evaluated in clinical trials that compared the drug to a placebo. Very few of the drugs have been compared directly to one another. So, in 2019, Huhn and his team published a meta-analysis, in which they reviewed over 400 studies of antipsychotics for individuals with schizophrenia and compared the side effect profiles of each drug.

While all of the drugs were different, the team found that patients who took the older, first generation antipsychotics were more likely to report motor side effects and high levels of prolactin—a molecule that lowers to production of sex hormones estrogen and testosterone. The newer antipsychotics are more likely to cause sedation. 

Of the 400 studies included in the review, only 10 included measures of patient-reported quality of life, which is unfortunate, he noted, because quality of life is a way of measuring both safety and efficacy together.

Do Antipsychotics Cause Weight Gain?

Yes, weight gain can be a side effect of antipsychotics. This particular side effect is more common with the newer antipsychotic drugs than the older ones. Olanzapine (Zyprexa) is likely to cause larger amounts of weight gain (an increase of more than 7%) than risperidone (Risperdal) or paliperidone (Invega), though these two can also cause weight gain, according to a 2018 meta analysis

Buch says that in addition to alerting your physician if you’re gaining weight, you should get regular blood draws to test your glucose levels. Your provider may suggest you switch your medication.

Are Antipsychotics Safe in Pregnancy?

If you’re pregnant, you should discuss all prescriptions and supplements with your healthcare team before making any change to your regimen. For most drugs, there are both risks and benefits to stopping use while you’re pregnant. For example, if you stop taking antipsychotics, both you and your fetus could be at risk due to exposure to your untreated symptoms or excess stress.

In most cases, only a small number of studies have looked at pregnancy outcomes, and you and your physician will have to make decisions with the, albeit small, amount of information that is available. Mother To Baby, an organization that studies the safety of drugs in pregnancy and provides information to people and doctors, has fact-sheets that describe what is and isn’t known about three different antipsychotics in pregnancy and breastfeeding:

Tardive Dyskinesia

Many side effects of antipsychotics actually wane over time as your body adjusts to the drug, but tardive dyskinesia, a movement disorder characterized by repetitive, uncontrollable muscle movements, is more likely to develop after you’ve been on the drug for months or years. Exercise may help you control your muscles and balance.

Your healthcare provider might also suggest switching to another antipsychotic medication, but if the one you’re using is otherwise tolerable and working well for you, your doctor may instead recommend additional drugs to treat the side effect. 

Typically, when a physician prescribes a medication to treat the side effect of another medication, it’s called a prescription cascade. While the situation is not ideal, psychosis is dangerous and, in some cases, the additional drugs may be necessary to maintain your quality of life as you continue taking the antipsychotic to prevent psychosis.

What You Can Do About Antipsychotic Medication Side Effects

If you are taking antipsychotics to manage depression, bipolar disorder or anxiety, you may be able to stop taking the drugs and explore other treatment options. However, if you have schizophrenia, you may need to take antipsychotics for most of your life, explains Buch.

“Side effects are also quite dose dependent,” says Huhn. You can lower the dose and feel fewer side effects. There aren’t many known withdrawal symptoms from antipsychotics. You may have trouble sleeping if the drug has helped sedate you. However, there is a high risk of psychosis.

It’s crucial that the physician lowers your dose very gradually and carefully, because treatment at too low a dose could leave you vulnerable to another psychotic episode. According to a 2020 Cochrane Review of 75 randomized controlled trials in which some patients received antipsychotics while others received placebos, this can be very dangerous. 

You could even become aggressive or attempt to take your own life. Still, Huhn emphasizes that “it’s very often possible to reduce doses,” and lessen side effects over time. 

Starting On An Antipsychotic Drug

Many people who are prescribed antipsychotics will need to take them long term or even for their entire lives. At first, a doctor will usually prescribe a low dose and gradually raise it until it has the desired effect. Huhn suggests that the treatment and side effects can change over time. Many side effects dissipate as your body adjusts to taking the drugs.

“What I quite often do is I start by prescribing some drugs that are effective and that are also sedative, because then the patient calms down,” he says. But once the patient is calmer and able to engage in therapy and healthy coping mechanisms, he’ll change the prescription because he doesn’t want the patient to remain sedated in the long term. Feeling too tired to work is a common complaint among patients that stay on drugs with sedative effects.

Antipsychotics and Alcohol, Caffeine, or Nicotine

Antipsychotic drugs can interact with many other substances including coffee, alcohol, or nicotine. Even supplements or foods can change the effectiveness of medications. 

If you start drinking more coffee, you may need a slightly lower dose of your antipsychotics, because caffeine keeps the drugs in your body longer. 

Nicotine, on the other hand, increases the speed at which your body breaks down antipsychotics, so if you smoke, you may need a slightly higher dose.

Antipsychotics can enhance the effects of alcohol, so if you choose to drink, you should do so very slowly and pay attention if you start to get dizzy or drowsy.

Do Antipsychotics Cause Sexual Dysfunction?

Yes, some antipsychotics can make it difficult to enjoy sex and for men to get erections. For men, taking Viagara (sildenafil) can help, but it can also cause headaches and nasal congestion. Researchers emphasize that more work needs to be done to understand sexual dysfunction wth antipsychotics, but that some drugs are more likely to cause this side effect than others, and you’re experiencing sexual side effects from antipsychotics, you should bring it up to your doctor and discuss the possibility of switching your medication.

How to Talk to Your Doctor About Antipsychotics

The very first question you should ask your physician is why you need antipsychotics. Find out if they’re being prescribed to treat psychosis or another condition, such as depression or insomnia. If it’s for other conditions, you should ask if there are any alternatives.

As with any medication, you should ask what the most common side effects are and if there are any dangerous ones you need to watch out for. Ask your doctor about the specific medication being prescribed, and if there are any alternatives that might cause you fewer of the side effects that are most important to you.

Lastly, bring a list of any other medicines you’ve been prescribed that didn’t work or that caused side effects you didn’t like. 

“That’s very, very helpful for the doctor,” says Huhn. Having a comprehensive list of your current medications (both prescription and over-the-counter) can also help your doctor determine possible interactions.  

Lifestyle Changes That Can Reduce the Risk of Psychosis

In addition to taking antipsychotics, there are some lifestyle changes that can reduce your risk of experiencing another psychotic episode. They include:

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