Antipsychotics

What Are Antipsychotics?

Antipsychotics are prescription psychotropic medications used primarily to treat psychotic disorders, which include:

• Schizophrenia
• Bipolar disorder
• Schizoaffective disorder

Some antipsychotic uses include helping reduce hallucinations and delusions, decreasing paranoid thinking, and providing mood stabilization.

How Do Antipsychotics Work?

Antipsychotic medications work primarily by blocking dopamine receptors. The more strongly a medication binds to a dopamine receptor, the more potent its effects. There are four main pathways in the brain involving dopamine:

• The mesolimbic pathway mediates pleasure and reward.
• The mesocortical pathway manages cognition, emotion, decision-making, and concentration.
• The nigrostriatal pathway is involved in movement and motor planning.
• The tuberoinfundibular pathway regulates prolactin secretion, which is important in fertility, libido, and bone health.

Schizophrenia is a disorder composed of positive and negative symptoms. Antipsychotic medications work on dopamine and help reduce positive symptoms through the mesolimbic pathway. Positive symptoms involve the production of symptoms and include:

• Hallucinations
• Delusions
• Disorganized thinking and speech

Visual hallucinations, for example, involve seeing things that are not there. The positive symptoms of schizophrenia are thought to be due to the increased activity of dopamine in the mesolimbic pathway.

Negative symptoms involve the absence of elements that are usually present and include:

• Flattening of emotions
• Absence of thought and speech
• Reduction in initiation and drive
• Social isolation

Individuals who do not have schizophrenia experience a wide range of emotions from day to day, but individuals with schizophrenia tend to express very little emotion, if any, known as a flattening of affect. The negative symptoms of schizophrenia are thought to be due to decreased activity of dopamine in the mesocortical pathway.

Antipsychotics are effective at reducing the positive symptoms of schizophrenia. The negative symptoms of schizophrenia are more challenging to treat and do not improve as much, although newer developments in these medications are aimed at better targeting these symptoms.

Clozapine is one of the few antipsychotics that has shown some benefit in improving the symptoms of:

• Anhedonia (loss of pleasure/enjoyment)
• Alogia (decrease in thought and speech)
• Avolition (loss of drive, motivation, and initiative)
• Flattening of affect (blunting of experience and expression of emotions)

Improvements in antipsychotic medications increase how specifically they block dopamine receptors to produce positive effects while decreasing negative side effects. Most antipsychotics also have varying degrees of effect on histamine, muscarinic, and serotonin receptors. Effects on histamine and muscarinic receptors cause some of the known side effects of antipsychotics, such as sedation, lightheadedness, dry mouth, constipation, and urinary retention. Olanzapine and quetiapine are significantly sedating and help with insomnia. They are also very likely to cause weight gain. The counterbalancing effects on serotonin receptors are thought to decrease the likelihood of movement disorders.

What Different Types Of Antipsychotics Are There?

Antipsychotic medications are organized into two groups: first-generation, or typical antipsychotics, and second-generation, or atypical antipsychotics.

First-Generation Antipsychotics

First-generation medications are as effective as second-generation options but are much more likely to cause movement disorders. For this reason, second-generation medications are typically used first-line, and first-generation ones are reserved for treatment-resistant conditions.

First-generation antipsychotics can be further divided into low-potency and high-potency medications. Low-potency antipsychotics have therapeutic doses in the hundreds of milligrams and work more at the histaminic and muscarinic receptors compared to dopamine receptors. As a result, they have less tendency to cause abnormal movement side effects but are more likely to cause sedation and other side effects, including:

• Dry mouth
• Constipation
• Difficulty urinating
• Blurry vision
• Drowsiness

Some common low-potency antipsychotics include chlorpromazine and thioridazine.

High-potency antipsychotics have the opposite ratio of effects compared to low-potency ones. Therapeutic dosages are in the tens of milligrams, and high-potency antipsychotics work less at histaminic and muscarinic receptors compared to dopamine receptors. They are, therefore, much less likely to cause sedation and weight gain but have a very high risk of causing abnormal involuntary movements. Some common high-potency antipsychotics include fluphenazine, haloperidol, loxapine, perphenazine, and pimozide.

Haloperidol is one first-generation antipsychotic medication that is still used frequently as an emergency medication for acute agitation in the hospital. It is not only used in inpatient psychiatric wards but also in critical care units where very sick patients experience confusion and agitation secondary to their medical conditions. It is very effective and available in many different formulations, including an injection that rapidly acts to produce a calming effect in a combative patient.

Second-Generation Antipsychotics

Second-generation antipsychotics are generally considered equally effective to first-generation antipsychotics, apart from clozapine, which has been shown to be superior in treatment-resistant schizophrenia. They have a similar mechanism of action, except for a few newer options that partially increase dopamine receptor activity, such as aripiprazole, brexpiprazole, and cariprazine.

Second-generation also block serotonin receptors more when compared with first-generation medications, which is thought to partially explain the reason for the lower risk of movement disorders in second-generation antipsychotics.

The medications in this class include:

• Aripiprazole
• Asenapine
• Brexpiprazole
• Cariprazine
• Clozapine
• Iloperidone
• Lumateperone
• Lurasidone
• Pimavanserin
• Paliperidone
• Quetiapine
• Risperidone
• Ziprasidone
• Olanzapine

Antipsychotic medications can be very versatile and are used to treat a wide range of conditions. Their use is not limited to only psychotic conditions but also includes depressive disorders, anxiety disorders, and non-psychiatric conditions.

What Conditions Do Antipsychotics Treat?

The primary conditions that antipsychotics treat are psychotic disorders including:

• Schizophrenia
• Bipolar disorder
• Schizoaffective disorder
• Major depressive disorder, which, when severe, can present with psychotic features

These medications can also be used to boost antidepressants in the treatment of major depressive disorder, even in the absence of psychosis. They are also used to treat:

• Aggressive behaviors in dementia
• Agitation and delirium in the intensive care setting
• Delusional parasitosis
• Insomnia
• Treatment-resistant OCD
• PTSD
• Psychosis in Parkinson’s disease
• Hiccups
• Chemotherapy-induced nausea and vomiting
• Postoperative nausea and vomiting
• Substance intoxication resulting in agitation/aggressive behaviors
• Irritability associated with autism spectrum disorder
• Tourette syndrome

This list is not intended to be exhaustive, and new uses are discovered for antipsychotic medications every day. They are a very effective class of psychiatric medication that offers a lot of benefits to individuals suffering from serious mental illnesses.

What Are The Benefits Of Antipsychotics?

Antipsychotic medications can significantly reduce many psychotic symptoms that interfere with daily life. They decrease the impact of hallucinations, and many times hallucinations can completely resolve. Individuals become less preoccupied with delusional thoughts and have more flexibility and clarity in their thinking. An antipsychotic medication can be the difference between frequently being hospitalized to being able to maintain a steady job.

Antipsychotics do not only treat psychosis but can also help boost the effect of antidepressants to bring an individual to complete remission of their major depressive disorder, OCD, or PTSD. In comparison to antidepressants, you may see benefits from antipsychotics in the treatment of depression and anxiety in a much shorter timeframe, within a couple of weeks.

What Are The Disadvantages Of Antipsychotics?

Side effects of antipsychotics come from the effects on the nigrostriatal pathway (which leads to movement-related side effects) and the tuberoinfundibular pathway (which leads to effects on prolactin).

The most significant disadvantage of this class of medications is the side effect of weight gain. Some antipsychotics are much more likely to cause significant weight gain, but even the ones that are intended to be weight-neutral can still cause weight gain. There is also an increase in the risk of metabolic syndrome, which is the trifecta of elevated blood pressure, diabetes, and high cholesterol.

Despite advances in second-generation antipsychotics, there is still a risk of the development of abnormal involuntary movements. Most are reversible and treatable with discontinuation of the offending agent. There is an irreversible movement disorder called tardive dyskinesia, a late effect of medications that block dopamine. This disorder causes the production of involuntary movements, most commonly in the mouth and tongue, but can affect the arms, legs, trunk, and muscles used in breathing.

Tardive dyskinesia has become less common with the advent of newer antipsychotics and a better understanding of its causes. While it is still considered irreversible, it can be treated if caught early.

Who Can Prescribe Antipsychotics?

Antipsychotic medications are usually prescribed by psychiatrists, who have the expertise and understanding to safely select a medication that will have limited interactions with your other medications and tailor the choice to your specific symptoms.

Primary care physicians can also prescribe antipsychotics, and the number of prescriptions from non-psychiatrist physicians has been increasing in recent years.

Are Antipsychotics Commonly Prescribed?

A 2020 study from the BMC Psychiatry journal pooled data from the National Health and Nutrition Examination Survey estimating antipsychotic use in the United States at 1.7% (or 3.8 million adults).

Antipsychotic medications are commonly prescribed for off-label use, with approximately one-third of survey respondents taking them for major depressive disorder, 26% for bipolar disorder, and 10% for schizophrenia. A total of 17% reported antipsychotic use for sleep disorders.

How Long Can I Stay On Antipsychotics?

For many individuals, these medications are the mainstay of treatment and vital to continued positive effects. For those with bipolar disorder, schizophrenia, and schizoaffective disorder, antipsychotic medications are necessary to maintain stability and prevent hospitalization.

Untreated schizophrenia can lead to structural brain damage over time. Attention, memory, and verbal IQ may decline. Radiographic imaging of chronic schizophrenia shows widespread thinning of the cortex, most prominently in the frontal and temporal lobe areas. Imaging also shows the smaller volumes of the hippocampus, amygdala, and thalamus, among other brain structures, involved in memory and executive functioning of the brain, regulating organization, planning, multi-step processes, and attention.

In chronic psychotic conditions, long-term antipsychotic medications may be necessary for social and occupational functioning. Discontinuation of these medications often leads to a return of psychotic symptoms and the need for rehospitalization. Therefore, it is often recommended that individuals with these conditions remain on their medications for years, if not their entire lives.

Antipsychotic medications do have potential long-term negative effects on physical health due to effects on weight and increased risk of high blood pressure, high cholesterol, and diabetes.

However, in one of the largest nationwide follow-up studies of antipsychotic discontinuation in first-episode schizophrenia, patients who remained on antipsychotic medications had a 60% lower risk of death compared to those who discontinued, which supports theories that suggest antipsychotic medications provide protection to the brain in chronic psychotic conditions.

In individuals taking antipsychotic medications for indications outside of psychotic disorders, a typical recommendation is to continue the medication for 9-12 months, and if the condition remains stable at that point, it would be reasonable to discuss gradually tapering off the medication with your doctor.

Can I Work Or Drive If I’m Taking Antipsychotics?

Antipsychotics are safe to take and carry on with your usual daily activities. However, when you are first starting your medication, you may need to wait until you fully understand how the medication affects you before driving and operating heavy machinery.

Some medications in this class are sedating and may make you very sleepy. These medications are usually taken before bedtime, and by morning, the drowsy effects should be mostly gone. While you are adjusting to the medication, there may still be some lingering effects of drowsiness in the daytime. Most of the time, this side effect should improve over the course of a couple of weeks. If you find that you cannot stay awake throughout the day on your medication, speak with your doctor about whether a dose adjustment or change in medication is needed. These medications are meant to enhance your functioning, not limit it.

It is also a good idea to start your medication over a weekend so you can see how it affects you before you return to work.

Antipsychotics are meant to improve clarity of thought, but some individuals may feel like their thoughts are slowed down and have a harder time thinking. If you experience this effect, contact your doctor to discuss whether a dose adjustment or medication change is indicated.

Who Can’t Take Antipsychotics

There are very few contraindications to taking an antipsychotic medication. The primary contraindication is having an allergy to the medication or a component of the formulation.

Individuals taking large amounts of central nervous system (CNS) depressants such as benzodiazepines and opioids should avoid first-generation antipsychotics due to concerns about restricted breathing.

Caution should be exercised in individuals with the following conditions:

• Narrow-angle glaucoma
• Impaired kidney function
• Liver damage
• Myasthenia Gravis
• Severe cardiac abnormalities
• History of tardive dyskinesia
• Seizure disorder
• Severe respiratory conditions
• Gastrointestinal motility issues
• Urinary tract conditions
• Lewy Body dementia and Parkinson’s disease

There is a black box warning on all antipsychotic medications for use in older individuals with dementia. There is an increased risk of mortality from heart-related and infectious-related causes.

When Should I Call My Healthcare Provider?

You should contact your doctor if:

• You develop a rash, shortness of breath, facial swelling, or other signs that you may be having an allergic reaction to your medication.
• You feel extremely drowsy and cannot stay awake throughout the day.
• You find it difficult to think clearly.
• You develop new or worsening thoughts of suicide.
• You experience new or worsening involuntary movements, particularly those involving the mouth and tongue, as this could indicate an irreversible movement disorder.
• You experience high fever, muscle stiffness, and confusion, as this could indicate neuroleptic malignant syndrome, a rare life-threatening condition that can occur when starting antipsychotics and other medications that block dopamine receptors.
• If it has been 4-6 weeks since starting your medication and you are not noticing any improvement in your symptoms, contact your doctor to discuss the next steps in treatment. The time to respond depends on the specific condition. In bipolar disorder, symptoms can improve over several weeks. In schizophrenia, it typically takes months for symptoms to start improving.

If you have any concerns about your antipsychotic medications, don’t hesitate to contact your healthcare provider.

Treatment Options Are Available

Antipsychotic medications play a beneficial role in the management of a broad range of psychiatric and non-psychiatric conditions. They can have a significant impact on functioning that allows individuals with severe psychotic symptoms the ability to work and maintain relationships.

If you or a loved one is suffering from hallucinations, delusions, paranoia, or very severe depression and anxiety, an antipsychotic medication could be beneficial in your treatment. Speak with your doctor about your mental health treatment options, and you could be on your way to feeling better.