Antipsychotic Medications With The Least Side Effects

Antipsychotic medications are used to treat mental illnesses. Just like any medication, antipsychotics’ side effects may affect people differently. However, some agents are known for the extent of specific side effects, such as weight gain or sedation. Understanding this fact plays a vital role in treatment success. Please continue reading to learn which medications are best tolerated and the side effects to watch out for during treatment.

What conditions are antipsychotic medications used to treat?

Antipsychotic medications are prescribed to treat the symptoms of schizophrenia, bipolar disorder, and even depression. Schizophrenia is a psychiatric condition that causes psychotic episodes in which there is a disconnection from reality. The two main symptoms of psychosis are delusions characterized by an unshakable belief in things that are not true, and hallucinations when a person hears voices or sees things that aren’t there. Other symptoms of psychosis include paranoia (suspiciousness), trouble thinking clearly, intense ideas, confusion, and difficulty communicating, leading to a decline in self-care and well-being.

Many of these symptoms can overlap with schizotypal personality disorder, a mental health disorder characterized by unusual behaviors, paranoia, and an intense discomfort with social situations and close relationships. Keep in mind that schizophrenia is not a personality disorder.

There are other causes of psychosis besides schizophrenia, including substance use and other medical conditions.

Antipsychotic treatment is the mainstay of medication management of schizophrenia. Antipsychotic drugs are also used to treat psychosis associated with mental health conditions such as major depressive disorder, severe agitation or anxiety disorders, bipolar disorder, Alzheimer’s disease, and substance-induced psychotic disorder. Due to their effects on a brain chemical called dopamine, antipsychotics may also be prescribed to reduce tics in people with Tourette syndrome.

Antipsychotic medications work by balancing the levels of certain natural chemicals in the brain. These drugs are available in oral tablet form as well as long-acting parenteral forms, including injections into a muscle or under the skin. Even though antipsychotics do not cure the conditions, they are very effective at keeping the symptoms under control, which can ultimately help people maintain a normal life. Most antipsychotics take a few weeks or even months to reach their full effect.

While taking antipsychotics can be very beneficial for people with psychosis, these drugs can cause serious side effects. In each individual patient, one antipsychotic medication may be better tolerated than another. The aim of treatment is to control psychotic symptoms while minimizing adverse effects.

What are the different types of antipsychotic medications?

Antipsychotics are broadly classified as follows:

First-generation (typical) antipsychotics

First-generation antipsychotics (FGAs) work by blocking dopamine receptors in the brain. Examples of first-generation (conventional or typical) antipsychotics include chlorpromazine (Thorazine), haloperidol (Haldol), fluphenazine (Modecate), thiothixene (Navane), trifluoperazine (Stelazine), thioridazine, pimozide (Orap), and molindone (Moban).

Second-generation (atypical) antipsychotics

Second-generation antipsychotics (SGAs) are newer antipsychotics. They block dopamine receptors as well as serotonin receptors in the brain. Examples of atypical antipsychotic agents include clozapine (Clozaril), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), asenapine (Saphris, Secuado), lurasidone (Latuda), iloperidone (Zomaril), lumateperone (Caplyta), and paliperidone (Invega).

What are the common side effects of antipsychotic drugs?

The side effect profile is the biggest difference between FGAs and SGAs. FGAs are known for their drug-induced movement disorders, especially at high doses, while SGAs are more likely to cause metabolic changes leading to weight gain. However, the two classes share a wide range of overlapping side effects, which are listed below:

Dry mouth, blurred vision
Constipation
Drowsiness
Agitation, restlessness
High blood sugar, leading to an increased risk of diabetes
Sexual dysfunction
Movement disorder
Cardiac issues causing prolonged QT interval, an irregular heart rhythm disorder

First-generation antipsychotics are known for causing extrapyramidal symptoms, which are movement disorders causing involuntary movements that you cannot control. Examples of extrapyramidal symptoms include akathisia (an uncontrollable urge to move or fidget) and dystonia (involuntary muscle contractions). Long-term use of typical antipsychotics can lead to tardive dyskinesia (abnormal, uncontrolled, repetitive movements of the face, torso, and other parts of the body). FGAs can also cause Parkinsonism with symptoms similar to Parkinson’s disease, causing tremors, stiff facial muscles, and problems with speaking and finishing thoughts.

While atypical antipsychotics (second-generation antipsychotics) are less likely to cause movement disorders, SGAs can increase the risks of metabolic disorders, weight gain, increased cholesterol levels, insulin resistance, and diabetes.

What is the best tolerated antipsychotic?

Evidence suggests that second-generation drugs (atypical antipsychotics) are better tolerated than first-generation (conventional or typical) antipsychotics. Second-generation antipsychotics have, therefore, been replacing first-generation drugs as the treatments of choice.

What is the least harmful antipsychotic drug?

Different antipsychotics are more likely to cause different side effects:

Weight gain: Most likely: clozapine and olanzapine. Least likely: ziprasidone, lurasidone, and aripiprazole.
Movement disorders: Most likely: risperidone, haloperidol, and paliperidone. Least likely: ziprasidone, olanzapine, and clozapine.
Sedation: Most likely: clozapine, quetiapine, and olanzapine. Least likely: ziprasidone and aripiprazole.
Cardiac issues (mostly prolonged QT interval): Most likely: thioridazine, ziprasidone. Least likely: clozapine, olanzapine, and risperidone.

Which antipsychotic has the least metabolic side effects?

Second-generation antipsychotics can cause weight gain, leading to an increased risk of metabolic syndrome (high blood sugar, high blood pressure, and high cholesterol). Metabolic syndrome is associated with an increased risk of diabetes, heart disease, and stroke. Studies have shown that the average weight gain with standard doses of atypical antipsychotics for 10 weeks is 4.15 kg with olanzapine and 4.45 kg with clozapine. Other antipsychotics, such as ziprasidone and aripiprazole are less likely to cause weight gain and metabolic side effects.

Which antipsychotic is best for schizophrenia with least side effects?

First-generation antipsychotics are effective in treating the positive symptoms of schizophrenia (hallucinations, delusions, repetitive movements), but they are ineffective in treating the negative symptoms (emotional blunting, social withdrawal, apathy, difficulty communicating).

Atypical antipsychotics (second-generation antipsychotics) can effectively treat both negative and positive symptoms of schizoaffective disorders and are the preferred treatment, with clozapine probably being the most effective antipsychotic.

In addition, the risk of extrapyramidal side effects and complications such as neuroleptic malignant syndrome is lower with second-generation antipsychotic drugs compared to first-generation (older) drugs.

How to manage side effects from antipsychotics?

Treating psychosis requires long-term treatment. If you have been diagnosed with schizoaffective disorder or other mental illnesses with psychotic features, your healthcare provider may start you on an antipsychotic drug. If there is no improvement in your symptoms after a few weeks or you have intolerable side effects, they may adjust your dose, prescribe medications to manage the side effects or change you to other medications.

Always read the patient information leaflet and take an antipsychotic drug exactly as prescribed. If you have severe side effects from antipsychotics, tell your doctor. Do not stop taking antipsychotics suddenly, as this can lead to withdrawal effects. Withdrawal symptoms may include stomach pain, nausea, vomiting, diarrhea, headache, fast heart rate, sweating, dry mouth, muscle aches, restlessness, anxiety, insomnia, and severe agitation.

Keep in mind that you can also control symptoms and improve your quality of life with natural remedies such as sucking on ice chips or sugarless candy to relieve dry mouth, eating a healthy diet and getting regular exercise to prevent weight gain, and getting up slowly from a sitting or lying position to prevent dizziness. Antipsychotics with sedating side effects can be used at bedtime to help with sleep; they may also be beneficial for patients with acute agitation, severe anxiety, or mania.

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