Antipsychotics

What are antipsychotics?

Antipsychotics are a group of medications that are often used to treat schizophrenia and psychosis, in particular hallucinations and delusions ^[1].

Hallucinations often involve seeing or hearing things that are not really there, but can involve any of the five senses. Delusions are a strong belief in something that is not based in reality or shared by others, which sometimes involves paranoid ideas.

Delusions and hallucinations are referred to as positive symptoms of schizophrenia and are often the most noticeable signs of a psychotic episode. Antipsychotics are often very effective at treating positive symptoms, but may be less effective at treating negative symptoms of schizophrenia, which can include social withdrawal, impaired concentration, and low mood ^[2].

Antipsychotic medications are categorized as typical and atypical antipsychotics, all of which work in similar ways but have different effects depending on the condition and the individual’s response to the medication ^[3].

The aim of antipsychotic medication is to effectively treat the symptoms of the individual’s condition, with few unpleasant side effects.

People who require antipsychotic medication may need to try more than one treatment before finding one that works well for them ^[4].

Types of antipsychotic medication

Antipsychotic medications can be taken as a tablet, capsule, liquid, or injection. They can be used to manage acute episodes of psychosis, for which they might only be required for a short time, or in other cases, they may be used to manage chronic conditions such as schizophrenia and can be required for long-term or lifelong use ^[1].

Some people who require long-term antipsychotic treatment might be prescribed a depot injection, which is usually administered every 2-4 weeks. This can help reduce the need to remember daily medication, improve compliance, and reduce hospitalization ^[4].

How antipsychotics work

Most antipsychotic medications work by affecting the neurotransmitter called dopamine, which is often referred to as the ‘pleasure chemical’ of the brain, as it is responsible for the pleasure response experienced by food, sensory experiences, and illicit drugs. Dopamine also affects movement, sleep, memory, cognition, and learning ^[5].

When dopamine is overactive in the brain it can lead to psychotic symptoms, such as hallucinations and delusions. Antipsychotic medications impact dopamine by reducing its activity and transmission, to regulate and reduce these symptoms ^[1][6].

Typical and atypical antipsychotics

Antipsychotics are categorized as typical and atypical antipsychotics, also known as first-generation and second-generation. Typical, or first-generation, antipsychotics were produced as the first treatment for psychosis, but were found to often cause serious side effects. Following this, atypical, or second-generation, antipsychotics were created and generally cause fewer side effects ^[3].

While typical antipsychotics affect only dopamine, atypical antipsychotics affect both dopamine and serotonin, which is a neurotransmitter responsible for mood regulation. Because of this, atypical antipsychotics can not only reduce positive symptoms, but have also been found to be effective at managing negative symptoms and mood dysregulation ^[3][6].

The effect of atypical antipsychotics on serotonin is also believed to be responsible for the reduction in side effects of this generation of medications, particularly extrapyramidal side effects related to movement ^[6]. As such, atypical antipsychotics are now more commonly prescribed than typical antipsychotics, although they can sometimes cause other side effects, such as weight gain ^[1].

Typical antipsychotics include chlorpromazine, haloperidol, loxapine, pimozide, and thiothixene.

Atypical antipsychotics include risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone.

Clozapine

Clozapine is an atypical antipsychotic but works differently from all other antipsychotic medications. It is known to be very effective at managing the symptoms of schizophrenia, with few of the usually seen side effects of antipsychotics. However, it does also carry the risk of serious physical health complications ^[2].

Clozapine can cause serious heart issues including rapid heart rate and can also cause low white blood cell count, which increases the risk of infection and serious health issues, and can be fatal ^[7].

Because of these risks, clozapine is only prescribed if at least two other antipsychotic medications have been prescribed for treatment of schizophrenia and were ineffective ^[1]. When it is prescribed, doctors are required to closely monitor physical health to ensure the safety of the individual and must stop clozapine treatment if serious side effects occur.

Side effects of antipsychotics

The side effects caused by antipsychotics can vary depending on the medication, and people may have differing responses to the various medications ^[4]. Often when starting a new medication, it is common to experience side effects as your body adjusts to the medication, but they will typically subside within a few weeks.

Common side effects of antipsychotics include ^[1][8]:

• Dizziness
• Dry mouth
• Blurred vision
• Sedation
• Stomach upset, such as nausea and vomiting

However, some side effects can be more serious or persistent and can cause concern. It is important to contact your doctor immediately if you experience any concerning side effects from your medication, as you may need a reduced dose or a change of medication.

In general, first-generation (typical) antipsychotics cause more side effects than second-generation (atypical) antipsychotics, particularly side effects related to movement, known as extrapyramidal side effects, although all antipsychotic medications can cause these effects ^[7].

Some of the more serious side effects associated with antipsychotic medications include:

Metabolic syndrome

Metabolic syndrome includes weight gain, diabetes, high blood pressure, and high cholesterol, although not all of these symptoms need to be present for a diagnosis of metabolic syndrome. The risk of these symptoms occurring is increased by antipsychotic medications, so it is necessary to have regular physical health checks during treatment to monitor and regulate these risks ^[8].

Weight gain

Second-generation antipsychotic medications are more likely to cause weight gain than first-generation. Commonly, olanzapine and clozapine cause the most weight gain, by increasing appetite and causing sedation ^[7].

Increased prolactin

Antipsychotics can cause changes in hormone levels, particularly prolactin. Increased prolactin can lead to sexual dysfunction, such as decreased libido, breast tenderness, milk production and secretion, and irregular or missed menstruation ^[7][8].

Generally, second-generation antipsychotics are less likely to increase prolactin levels, aside from risperidone ^[3].

Neuromuscular effects

Antipsychotics can create side effects in the muscles, caused by decreased dopamine levels, such as stiffness, weakness, spasms, shaking or tremors, and restlessness ^[8].

These effects are more common with first-generation antipsychotics and with higher doses of medication ^[4].

Tardive dyskinesia

Antipsychotic medications have an effect on the nervous system, leading to symptoms known as tardive dyskinesia, which include abnormal, repetitive, and involuntary movements of the body or face, similar to tics ^[9].

Tardive dyskinesia is more common with first-generation antipsychotics and with prolonged use ^[5][7]. However, there are medications that can be prescribed to reduce these symptoms ^[9].

Neuroleptic Malignant Syndrome (NMS)

NMS is very rare but is a very serious, and sometimes fatal, neurological condition that can be caused by antipsychotic medications. Symptoms of NMS include severe muscle rigidity, organ failure, confusion, fever, and breathing difficulties. If NMS occurs, antipsychotic medication must be stopped immediately, and the condition treated ^[1][8].

NMS is more common with first-generation antipsychotics, but all antipsychotic medications can cause NMS ^[1].

Heart conditions

Antipsychotic medications can increase the risk of harm to the heart, including increased or irregular heartbeat and prolonged QT interval ^[7].

This risk is greater with first-generation antipsychotics but can occur with any antipsychotic medication ^[1].

Seizures

All antipsychotic medications can increase the risk of seizures, so they are generally not recommended for use in those with a history of epilepsy or seizures ^[8].

Glaucoma

All antipsychotic medications can increase the risk of glaucoma, a serious eye condition, so it is advised to have regular eye tests throughout this treatment to monitor any concerning changes in eye health ^[8].

What disorders are antipsychotics used to treat?

Certain antipsychotics are approved by the US Food & Drug Administration (FDA) to treat various conditions, depending on the specific medication, including ^[1][10]:

• Schizophrenia: Antipsychotics are generally effective at treating schizophrenia, as well as other psychotic disorders such as schizoaffective disorder, first episode psychosis, and drug-induced psychosis.
• Bipolar disorder: Various antipsychotics are used in the treatment of bipolar disorder, with or without psychotic symptoms. Typical antipsychotics are usually only prescribed for acute mania within the context of bipolar disorder, while atypical antipsychotics can be used to treat manic and depressive symptoms, and in the maintenance treatment of bipolar disorder.
• Depression: Some atypical antipsychotics can be prescribed to treat depression, with or without psychotic symptoms, particularly if the condition is treatment-resistant, and may be used as an adjunctive treatment for major depressive disorder, alongside an antidepressant medication.
• Tourette syndrome: Two typical antipsychotics, haloperidol and pimozide, are approved for use in the treatment of Tourette syndrome.
• Borderline personality disorder (BPD) with psychotic symptoms: Antipsychotics are approved for treatment if there is a presence of psychotic symptoms within borderline personality disorder, but not to treat personality disorders without psychotic symptoms.

Medications are also prescribed off-label, which means that the FDA has not approved these uses, but it has been deemed necessary for treatment by a medical professional.

Off-label uses of antipsychotic medications include ^[11][12]:

• Attention deficit hyperactivity disorder (ADHD)
• Posttraumatic stress disorder (PTSD)
• Personality disorders
• Eating disorders
• Obsessive-compulsive disorder (OCD)
• Anxiety disorders
• Insomnia
• Dementia (recent research has found that antipsychotic medications used to treat dementia in the elderly can increase the risk of stroke and fatality, so this use has become less common ^[13])

Alternative treatments for psychosis

Medications

As there are several different antipsychotic medications, you may need to try several before you find one that works well for you.

Depending on your condition and response to the medication, you may need more than one antipsychotic, or you might require other types of medication to help manage your condition, such as antidepressants, mood stabilizers, and anxiolytics ^[1][10].

Your doctor will help you find the right medication or combination of medications to manage your symptoms, and it is important that you take your medication exactly as prescribed, to prevent adverse effects.

Therapies

Talking therapies are often effective at managing mental health conditions, such as psychosis, alongside medicinal treatments. This could include ^[2][14]:

• Cognitive behavioral therapy: CBT can help you to gain a better understanding of your condition, manage your symptoms, and learn positive coping strategies to manage distress.
• Family therapy: It can be useful to engage in therapy alongside family members, so that they can gain a better understanding of your symptoms and condition, learn how they can best support your treatment, and receive support for any challenges they might face.
• Group therapy: It can be useful to speak with others who have had similar experiences, to help you learn skills to manage your symptoms, increase acceptance and understanding of your condition, and engage in positive social interactions.
• Social support: You may be assigned a social worker to help you manage any challenges you face in reintegrating socially or professionally following a psychotic episode and support you in regaining skills for independent living.

Self-care

You may be able to reduce the impact of your symptoms or prevent a reoccurrence of a psychotic episode by improving and maintaining your physical and mental wellbeing with self-help techniques, such as ^[2][4]:

• Healthy eating
• Avoiding drugs and alcohol
• Relaxation exercises
• Forming and maintaining a regular sleep pattern
• Engaging in regular exercise
• Consistently attending appointments with your doctor and mental health professionals
• Ensuring you follow advice and treatment plans