Antipsychotic Drugs

Welcome to this video tutorial over antipsychotics. Today we are going to discuss what exactly these drugs are, what they treat, and how to effectively use them. Be sure and check out our other pharmacology videos for information from other drug classes such as antihypertensives, antimicrobials, and diuretics.

Applications

Antipsychotics are chemical compounds used to treat a wide variety of psychotic disorders. Examples of these disorders include schizophrenia, bipolar disease, and depressive psychosis. There are also some unscripted uses for antipsychotics which we will discuss further on in the video.

According to the American Psychiatric Association, schizophrenia is diagnosed as a chronic brain disorder with symptoms that include delusions, lack of motivation, hallucinations, and unusual behaviors. This disorder can be disabling and is characterized by episodes where one is unable to distinguish between what is real and what isn’t. There is currently no cure for schizophrenia, however there is a lot of research that suggests improvement in symptoms with the use of antipsychotics.

People with bipolar disorders are shown to have some experience of a variety of manic episodes, such as decreased need for sleep, excessive talking, or increased involvement in activities with potentially painful consequences.

Antipsychotic therapy for these individuals has been shown to help this population lead a healthy and normal life.

Antipsychotics have also been helpful in reducing the symptoms associated with depressive psychosis. Depressive psychosis is different from regular depressive episodes due to the decreased ability to distinguish reality during times of increased depression. There are also several off-label uses for psychiatric medications. Patients with Tourette syndrome, Huntington’s disease, and uncontrollable vomiting have also benefited from antipsychotics.

The antipsychotic medications fall into two different groups. The first-generation antipsychotics have been around for several decades and more information is available regarding their mechanisms of action, uses, and adverse side effects. These are super effective in treating symptoms associated with psychiatric conditions however, they carry a high risk for serious adverse effects called extrapyramidal symptoms. The second-generation antipsychotics are newer and have only been around the last three decades. These medications have a lower risk of extrapyramidal symptoms but do increase the risk for neuroendocrine symptoms such as weight gain, diabetes, and dyslipidemia. Deciding which one to use is dependent on the individual patient’s medical history and expected outcome.

First-Generation Antipsychotics

Let’s first talk about the first-generation antipsychotics. These work by blocking various receptors within the central nervous system. They also block dopamine 2 receptors in the brain which help suppress symptoms of psychosis. As a result, side effects from these medications are a result of blocked dopamine, acetylcholine, histamine and norepinephrine receptors. Schizophrenia is the most therapeutic use for this generation of antipsychotics. The longer these medications are used in the schizophrenic patient, the risk of relapse decreases. The first-generation antipsychotics do come with a red flag. Extrapyramidal symptoms are a group of movement disorders that result from the effects of antipsychotic drugs on the central nervous system. To this day, little research has been found that explains this phenomenon, however, the blockage of dopamine 2 receptors is the suspected cause.

There are four types of extrapyramidal symptoms. The first three occur early in treatment therapy and include acute dystonia, parkinsonism, and akathisia. Acute dystonia movements are characterized by muscle contractions, repetitive movements, and abnormal postures. This can be both frightful and painful for the patient. Parkinsonism symptoms are similar to the manifestations of Parkinson’s disease in the elderly. With these movements, you will see drooling, tremors, rigidity, a shuffling gait and a stooped posture. Akathisia is another extrapyramidal symptom that refers to an “inner sensation” of being restless. All three of these types of movement disorders can be treated early in the antipsychotic therapy regimen with a variety of drugs, however the fourth reaction, tardive dyskinesia, occurs later in therapy and no current treatment options are available. Tardive dyskinesia movements involve the body, tongue and face. Lip-smacking movements, flickering tongues, and involuntary movements of the toes, fingers, and limbs are present. This can be a permanent reaction and risk is increased depending on the amount of time you are on the medication. Any of the above movement disorders need to be reported to the care provider with caution expressed to not discontinue the medication on their own terms. Continuing the medication as prescribed could prevent additional complications caused by withdrawal symptoms. Another important adverse effect to mention with first-generation antipsychotics is Neuroleptic Malignant Syndrome. This is a rare but serious condition and can lead to death without treatment. This disorder will cause a sudden high fever, diaphoresis, heart dysrhythmias, altered mental status, seizures, and coma. Treatment with Dantrolene and Bromocriptine can lower the detrimental effects of neuroleptic malignant syndrome and increase chances of survival. Other more common side effects are anticholinergic in nature and include dry mouth, blurred vision, orthostatic hypotension, constipation, and tachycardia.

Extrapyramidal Symptoms

There are four main first-generation agents still used today. These include Haloperidol (Haldol), Fluphenazine, Chlorpromazine, and Thioridazine. Haldol is one of the more potent agents and is used primarily for acute psychosis episodes associated with Schizophrenia. This is also the preferred agent for Tourette syndrome. Adverse effects associated with Haldol include extrapyramidal reactions, neuroendocrine effects, and a prolonged QT interval.

Fluphenazine is also used in schizophrenia and has the same adverse effects as Haldol but also includes gynecomastia, galactorrhea, and menstrual irregularities.

The lower-potency agents are Chlorpromazine and Thioridazine. Chlorpromazine can be used in the treatment of schizophrenia, schizoaffective disorder and in bipolar disorder and is highly effective. Some of the off-label uses of this medication include reduction of vomiting episodes, relief of intractable hiccups, and behavioral problems in children. Thioridazine is used as a last-resort and is reserved for treating schizophrenia in those patients who have not responded to other safer remedies and has a “black-box warning” for fatal cardiac dysrhythmias.

All the first-generation anti-psychotics have multiple drug interactions that are important to note. Use of central nervous depressants such as antihistamines, benzodiazepines, and barbiturates can cause the central nervous effects to intensify. Antiepileptic drugs such as Levodopa can counteract the antipsychotic effects of the drugs and make them ineffective. Lastly, the use of anticholinergic drugs can intensify the already anticholinergic effects of the anti-psychotics and cause urinary retention, constipation, visual problems, and tachycardia.

Second-Generation Antipsychotics

Second generation antipsychotics are the newer agents on the market and carry a lesser risk of extrapyramidal effects than first-generation antipsychotics. There is an increased risk of weight gain, diabetes, and dyslipidemia with these agents. Careful consideration is to be used in patients who are at a higher risk for endocrine problems such as diabetes and patients with cardiac disease. Each of the newer agents work in their own way and carry their own adverse effects. Let’s now explore some of the second-generation antipsychotics.

Clozapine is a second-generation agent and works by blocking serotonin and dopamine receptors. It’s best used in the treatment of schizophrenia and levodopa-induced psychosis. Adverse effects include seizures, diabetes, weight gain, and dyslipidemia. Clozapine does have a black box warning for agranulocytosis and myocarditis. This drug is to be used sparingly in the elderly and in patients with dementia.

Risperidone works by binding to multiple receptors in the central nervous system and improves the cognitive function in patients with bipolar disorder and schizophrenia. Adverse effects with this medication are mild and are generally well tolerated.

Paliperidone and Ziprasidone are both approved for the acute therapy of schizoaffective disorder and for the maintenance therapy of schizophrenia. Adverse effects of these drugs include somnolence, orthostatic hypotension, and rashes. These drugs are not to be used with other drugs that can increase the QT interval such as antiarrhythmics and tricyclics.

Quetiapine is indicated for schizophrenia, major depression and bipolar disorder. A “black box warning” exists for this drug due to the high suicide risk in children, adolescents, and adults with psychiatric disorders.

Other second-generation antipsychotics include Aripiprazole, Asenapine, and IIoperidone. Again, careful consideration with the drugs are needed in the high-risk metabolic patients due to their ability to increase triglycerides and weight gain.

Individualized Treatment

Now that we have discussed both classifications of antipsychotic medications along with their risks and benefits, an individualized treatment must be considered when deciding what medication best fits a patient’s care plan. Both first and second-generation agents are equally effective, except for clozapine which is researched to be the most effective, and risks and benefits of each drug must be considered. While the first-generation carry a higher risk for extrapyramidal symptoms, second-generations increase the risk of metabolic effects. First-generations are more cost-effective but second-generations are researched to work longer. The key to success with either route is adherence to the treatment plan. During initial therapy, patient teaching is essential. These drugs only work when taken as prescribed and must be taken on a regular schedule. Patients must be informed that it can take a full six to eight weeks before therapeutic effects are noted and that it may be a “trial and error” before the right agent is found. As with any other medication, informative teaching of adverse effects and accurate dosing information should be provided.

Let’s try some review questions to test our knowledge over the antipsychotics:

Review Questions

A 55-year-old man who is prediabetic and who just had a coronary bypass is prescribed a second-generation antipsychotic for the treatment of mania episodes in Bipolar disorder. What labs need to monitored frequently for this patient?

1. TSH
2. BUN/CR
3. CBC
4. HDL/LDL

A patient on antipsychotic drugs reports to the clinic with complaints of dizziness upon standing and light-headedness. The provider knows that:

1. This is a common side effect of antipsychotic drugs.
2. The patient should immediately stop taking the antipsychotic drugs to prevent further complications.
3. This complaint is not related to the use of antipsychotic drugs.
4. Send the patient to the emergency room.

Let’s try one more.

The nurse suspects a patient who has been on a long-term treatment with a first-generation antipsychotic is experiencing extrapyramidal symptoms. What action should the provider take?

1. Nothing. This is a common side effect of both antipsychotic agents.
2. Switch the patient to a second-generation agent if not contraindicated.
3. Have the patient go immediately to the emergency room for evaluation.
4. Discontinue the patient from all antipsychotics.

Thank you for watching this video over first-generation and second-generation antipsychotic agents.