Schizophrenia Treatment Using Loxapine

Psychopharmacological Approaches to Treat Psychopathology

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Psychopharmacological Approaches to Treat Psychopathology

Schizophrenia and its spectrum disorders are disruptive disorders that significantly impact the normal processes of the brain (Chien & Yip, 2013). These disruptive disorders are linked to significant abnormalities because they interfere with the ability to think. Patients may struggle to function normally when the symptoms of these disruptive disorders are not controlled or managed. However, proper diagnosis and treatment of these disorders under close supervision of a psychiatric mental health practitioner enable patients to thrive. There are different psychotropic agents used to treat patients with psychotic disorders like schizophrenia. Prompt initiation of pharmacological treatment for schizophrenia and other psychotic disorders is essential, particularly within five years of the first acute episode (Patel et al., 2014).

Pathophysiology of Schizophrenia

Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), schizophrenia refers to a syndrome characterized by a high relapse rate (>70%), mood problems, negative symptoms, and bizarre delusions and behaviors over a long duration (Chien & Yip, 2013). The pathophysiology of schizophrenia is based on abnormalities in neurotransmission in terms of a deficiency or excess of neurotransmitters. Most of the symptoms of this psychotic disorder are associated with abnormal activity at dopamine receptor sites. As shown in Figure 1, four dopaminergic pathways (mesocortical, nigrostriatal, mesolimbic, and tuberoinfundibular) are involved in the development of symptoms of schizophrenia. Low dopamine levels within the nigrostriatal pathway result in motor symptoms whereas a decrease or blockade of dopamine in the tuberoinfundibular pathway increases prolactin levels. While the mesolimbic pathway may play a role in the positive symptoms of this disorder, low dopamine levels in the mesocortical pathway generate cognitive deficits and negative symptoms.

Figure 1: Pathophysiology of Schizophrenia

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159061/

Psychopharmacological Medication Agent

Antipsychotic agents are commonly used to treat many schizophrenic patients, particularly within the first five years of the initial acute episode. Pharmacological therapy should be administered immediately if an acute psychotic incident occurs. One of the medications used for the treatment of schizophrenia is loxapine, which is a first-generation antipsychotic agent. According to Chien & Yip (2013), loxapine is a typical antipsychotic agent that helps to reduce positive symptoms of the condition by improving mood, thinking, and behavior. It belongs to a class of drugs known as antipsychotics. The drug is sold under different names depending on the administration route and dosage. For inhalation only, loxapine is sold under the brand names Adasuve and Loxitane. However, it is sold as Loxitane for oral intake. The appropriate FDA indication use for loxapine is to treat symptoms of schizophrenia.

Pharmacokinetics and Pharmacodynamics of Loxapine

As a dibenzoxazepine tricyclic antipsychotic agent, loxapine has a chemical structure that is akin to clozapine as shown in Figure 2. The drug has atypical characteristics, which implies that several considerations should be made in the treatment of negative symptoms. Some of these considerations include the propensity for or lack of motor side effects (Popovic, Nuss & Vieta, 2015). The pharmacokinetics and pharmacodynamics properties of this medication include receptor binding with a more potent 5-HT2A antagonism than olanzapine and clozapine. With regard to receptor occupancy, loxapine is effective in blocking D2 and 5-HT2A receptors at 10-100 mg/day. Loxapine not only has a higher affinity for D3 and D4 receptors compared to other dopaminergic receptors like D2 receptors. Moreover, the drug binds to histaminergic H1, noradrenergic, and cholinergic M1 receptors while its interactions with these systems could influence pharmacological effects linked to subduing aggressive behavior and calming.

Figure 2 – Chemical Structure

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391595/

Appropriate Dosing

Loxapine is essentially a tranquilizer that antagonizes serotonin and receptors, which manifests as calming effects and subdual of aggressive behavior. This drug is available in 5, 10, 25, and 50 mg and is available for oral, inhalation, and intramuscular administration (Popovic, Nuss & Vieta, 2015). The appropriate dosing for loxapine is an initial 10-25 mg PO q12 hour while maintenance is 60-100 mg daily divided q6-12 hours but not exceeding 250 mg/day. Inhaled loxapine of 5-10 mg up to 30 mg administered every 4 hours has been found to be safe and well-tolerated by many patients (Spyker, Riesenberg & Cassella, 2015). Given the small differences in drug concentration, a second dose of loxapine should be administered 2 hours after the first dose and repeated dosing after an interval of between 2 to 4 hours. For many schizophrenic patients, a dose of 20 to 60 mg is safe and suitable for maintenance therapy. It is recommended that the dosage for this drug is reduced to the lowest level of symptom control.

As noted by Medscape (2021), loxapine is not recommended for children. Loxapine falls under Pregnancy Category C, which implies that it should be used with caution if the benefits outweigh the risks. However, it should be avoided during breastfeeding. The signs and symptoms of overdose of loxapine are dependent on the individual patient’s tolerance and the amount ingested. Extended dialysis and early gastric lavage are considered a suitable treatment of overdose of this antipsychotic agent. This drug is contraindicated in patients who are hypersensitive to dibenzoxazepines or those in comatose or severe drug-induced depression.

An important implication of dosing regimen for any medication including loxapine is half-life, which refers to the duration of time necessary for the concentration of a particular drug or substance to reduce to half its initial dose in the body (Smith et al., 2018). Drug half-life is important in dosing regimen since a short half-life implies that a more frequent dose is required to avoid unnecessary concentrations and to maintain desired outcomes. Therefore, half-life helps to achieve optimal efficacy, patient compliance, and safety. When orally administered, the half-life of loxapine is 4 hours while the intramuscular and inhaled route is between 8-23 hours and 6-8 hours respectively (Popovic, Nuss & Vieta, 2015). Some potential adverse reactions or side effects of loxapine include drowsiness, weakness, insomnia, seizures, weight gain/loss, headache, nasal congestion, and constipation.

Necessary Considerations

The treatment of schizophrenia using loxapine requires consideration of comorbidities that can co-occur with the condition. Some of these comorbidities include substance use disorders, depression, panic, and obsessive-compulsive disorders. These comorbidities interact with psychotic symptoms in clinically significant ways and could result in adverse outcomes. Healthcare providers should also make legal and ethical considerations during treatment including the recommended dosage, patient education/consent, potential side effects, safety and efficacy concerns, and FDA recommended uses. Patient education is a critical consideration as it affects safety, efficacy, and compliance with medication. Some pertinent patient education considerations include drug interactions, potential side effects, clinical circumstances, and competency to understand information.