Schizophrenia is associated with increased mortality, with a shortened lifespan and standardised mortality ratios that are reported to be twofold to fourfold those in the general population.1,5

A study showed a reduction in life expectancy of 18.7 years for men and 16.3 years for women with schizophrenia.

A study showed a reduction in life expectancy of 18.7 years for men and 16.3 years for women with schizophrenia. The leading causes of premature death among people with schizophrenia are cardiometabolic diseases, suicide, and accidents.1,5

Diagnostic criteria

According to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition, to meet the criteria for diagnosis of schizophrenia, the patient must have experienced at least two of the following symptoms:2

  • Delusions
  • Hallucinations
  • Disorganised speech
  • Disorganised or catatonic behaviour
  • Negative symptoms.

At least one of the symptoms must be the presence of delusions, hallucinations, or disorganised speech. Continuous signs of the disturbance must persist for at least six months, during which the patient must experience at least one month of active symptoms (or less if successfully treated), with social or occupational deterioration problems occurring over a significant amount of time. These problems must not be attributable to another condition.2

Treatment recommendations

The updated recommendations from the British Association for Psychopharmacology recommend antipsychotic medication as the first line of treatment for psychosis. Initial doses should be below those typical in established illness but sufficient for efficacy, as demonstrated in studies of first-episode patients – that is, doses in the lower end of the licensed therapeutic range.3

In South Africa, schizophrenia is classified as a prescribed minimum benefit by the Council for Medical Schemes (CMS). The CMS treatment algorithm recommends the second-generation antipsychotic medication as first-line therapy for acute and/or the first episodes:4

  • Risperidone
  • Quetiapine olanzapine
  • Paliperidone.

Benzodiazepine is recommended as first-line adjunctive therapy. Evidence supports lorazepam used liberally to attenuate disruptive behaviour in the acute setting.4

All antipsychotics are associated with extrapyramidal symptoms, which can present as dysphagia (swallowing disorders), oesophageal dysmotility, or aspiration. Dysphagia is common among patients living with schizophrenia. If untreated it can increase the risk for aspiration pneumonia, airway obstruction (eg choking), or metabolic abnormalities that result from failure to thrive. Historical causes of sudden death in psychiatric hospitals included asphyxiation or choking.5

Most swallowing disorders in schizophrenia fall into one of two categories:6

1. Antipsychotic-induced swallowing disorders

2. Abnormal eating, defined as s defined as a behaviour that consisted of eating too quickly or taking inappropriately large boluses of food.

Rates of reporting dysphagia associated with antipsychotics ranged from 0.43% of adverse effect reports to 2.08% of adverse effect reports. Most reports occurred within the first six months of treatment, with the highest frequency occurring within the first month of therapy.5

Mechanisms of antipsychotic-induced dysphagia include an extrapyramidal adverse reaction because dopamine blockade can cause dysphagia or laryngospasm.5

Dysphagia has been associated with non-adherence to treatment. A study showed that 14% of patients with dysphagia delay doses, 8% missed doses and 4% discontinued treatment.7,8

Non-adherence is a huge challenge in patients with schizophrenia. Data from the Clinical Antipsychotic Trials of Intervention Effectiveness study showed that 74% of patients had discontinued medication within 18 months due to insufficient efficacy, intolerable side effects or other reasons.7

Nonadherence to the medication has a negative impact on the course of illness resulting in relapse, rehospitalisation, longer time to remission, and attempted suicide.7

Overcoming dysphagia

Orally disintegrating tablets (also called orodispersible tablets) provide a means by which oral medications are delivered via rapid disintegration of a tablet within the mouth facilitating passage through the upper aerodigestive system without the use of water to aid in swallowing. Rapidly dissolving tablets may facilitate safer and more consistent delivery of medication to swallowing-compromised patients.9

The American Food Administration defines an ODT as a ‘solid dosage form containing medicinal substances which disintegrate rapidly, usually within a matter of seconds, when placed upon the tongue’.7

ODT can be administered to any patient having difficulty swallowing. They are also recognized as mouth dissolvable, melt-in-mouth, fast-dissolving, rapid melts, or porous tablets.9

These are tablets that get dispersed or disintegrate when gets in a contact with saliva with the release of active drug, providing maximum drug bioavailability as compared to the conventional dosage form.

This dispersible property is given by the addition of super disintegrants to the dosage form, which releases the drug in the mouth increasing the bioavailability. Three different methods for the addition of disintegrants are used, they are intragranular (within the granules), extra granular (addition after granulation) and a combination of both processes.9

Patients with dysphagia show a strong independent preference toward the ODT preparation, rating it easier to swallow. These results suggest that ODT may provide benefit to patients with dysphagia by improving both compliance and ease of swallowing while not increasing the risk of airway compromise. More than 75% of the participants preferred the ODT formulation.7

Advantages of ODTs

Some advantages of ODTs include:10

  • Ease of administration to patients who cannot swallow
  • Improved adherence
  • No water needed
  • No chewing needed
  • Improved stability
  • Suitable for controlled/sustained release actives.
  • Allows high drug loading
  • Ability to provide advantages of liquid medication in the form of solid preparation.
  • Cost-effective
  • Rapid drug therapy intervention.
  • Best for a patent with oesophageal problems and have difficulties with deglutition tablets.
  • Have an acceptable taste and pleasant mouth feeling
  • Leave the minimum residue.

Risperidone formulations

Risperidone was first approved by the FDA for the management of acute schizophrenia in 1993 and for the long-term maintenance treatment of schizophrenia in 2002.10,11

Risperidone is available in a variety of formulations, such as oral tablets, oral solution, ODT, and as a powder for solution for long-acting injection (LAI). The LAI formulation of risperidone (RLAI) and ODT were both approved for use by the FDA in 2003. The ODT and conventional tablets showed bioequivalence with respect to the active moiety, risperidone, and 9-hydroxy-risperidone.10,11

REFERENCES:

1. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia. AJP, 2020.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, American Psychiatric Publishing, 2013.

3. Barnes TRE, Drake R, Paton C, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 2019.

4. CMS. Draft PMB Benefit Definition Guideline: Schizophrenia. https://www.medicalschemes.com/files/PMB%20Definition%20Project/DraftPMBDefGuideline_Schizoprenia_20190319.pdf

5. Course El, Alastanos JN, Bozymski KM and Toscano RA. Dysphagia with second-generation antipsychotics: A case report and review of the literature. Ment Health Clin, 2017.

6. Funayamaa M, Takataa T and Korek A. Choking incidents among patients with schizophrenia may be associated with severity illness and higher-dose antipsychotics. General Hospital Psychiatry, 2019.

7. Carnaby-Mann G, and Crary M. Pill swallowing by adults with dysphagia. Arch Otolaryngol Head Neck Surg, 2005.

8. Higashi K, Medic G, Littlewood KJ, et al. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol, 2013.

9. Hannan PA, Khan JA, Khan A, and Safiullah S. Oral Dispersible System: A New Approach in Drug Delivery System. Indian J Pharm Sci, 2016.

10. Kakar S, Singh R and Kumar S. Orodispersible tablets: an overview. Proteomics & Bioinformatics, 2018.

11. Madaan V, Bestha DP, Kolli V, et al. Clinical utility of the risperidone formulations in the management of schizophrenia. Neuropsychiatr Dis Treat, 2011.

12. Van Schaick EA, Lechat P, Remmerie BM, et al. Pharmacokinetic comparison of fast-disintegrating and conventional tablet formulations of risperidone in healthy volunteers. Clin Ther, 2003.