Clinical Overview: Treatment of Schizophrenia, Schizoaffective Disorders

Schizophrenia

Schizophrenia is one of the top 15 causes of disability worldwide. It is a chronic mental disorder in which the affected individuals have a disruption in thought process, perceptions, emotions, and social interactions.¹ Schizophrenia affects approximately 24 million people worldwide—or 1 in every 300 individuals.² 

Patients with schizophrenia have higher morbidity and mortality than the general population. Comorbidities such as diabetes, liver disease, and cardiovascular disease are possible contributors to premature death. The concomitant medical conditions are higher in this patient population and are typically undertreated, contributing to the higher mortality rate.¹

Symptoms

Symptoms of schizophrenia include positive symptoms, which are the presence of certain features, and negative symptoms, which are absence of normal behaviors and functions, such as decreased speech and/or cognitive impairment. Typically, the negative symptoms and cognitive impairment appear years before the positive symptoms and account for a large portion of long-term disability and poor functional outcomes.

Schizophrenia positive symptoms

• Hallucinations (visual, auditory, tactile)
• Delusions
• Paranoia
• Disorganized speech (e.g., frequent derailment or incoherence)

Schizophrenia negative symptoms

• Social withdrawal
• Anhedonia (inability to feel or express pleasure)
• Avolition (lack of motivation or ability to accomplish purposeful tasks)
• Flat affect
• Alogia (poverty of speech/decrease in verbal expression)
• Apathy (lack of interest or emotion)

Patients with schizophrenia may lack the ability to functional normally in society, with poor hygiene and self-care common. Therefore, schizophrenia can lead to patients being unsuccessful in maintaining full-time employment and having problems in their interpersonal relationships and social life. Patients with schizophrenia may experience communication problems, having trouble putting meaningful words together.^3,4

Cognitive impairment

• Deficits in attention.
• Poor verbal and learning memory.
• Reduced processing speed.
• Deficits in executive functions.
• Lower IQ.

Social and occupational dysfunction

• Low level of functioning in work, interpersonal relationships, and self-care.

Patients are typically diagnosed from adolescence to their early thirties. The symptoms tend to appear sooner in male than in female patients.¹

Schizoaffective disorder

Similar to schizophrenia, schizoaffective disorder is a chronic disabling mental disorder. It is a combination of schizophrenia symptoms and mood symptoms. There are 2 types of schizoaffective disorder:^5,6

• Bipolar type schizoaffective disorder
• Depressive type schizoaffective disorder

Patients with bipolar type experience both manic and depressive episodes, whereas patients with depressive type only experience depression but not mania. During the manic phase, patients experience high energy, grandiosity (exaggerated self-importance, knowledge, and ability), racing thoughts, increased risky behavior, pressured speech, and no to little sleep while still feeling rested.

Schizoaffective disorder is relatively rare (lifetime prevalence 0.3%). Similar to schizophrenia, men develop the illness at an earlier age compared to women. Many patients with schizoaffective disorder may be incorrectly diagnosed with bipolar disorder or schizophrenia.⁵

Etiology

Disorder etiology for schizophrenia and schizoaffective disorder is not well understood; however, genetics, brain chemistry/structure (imbalance in neurotransmitters), stressful life events/trauma, and illicit drug use may contribute to the development of schizophrenia/schizoaffective disorder.⁵ 

Treatment

The mainstay of treatment for schizophrenia and schizoaffective disorder includes antipsychotics.⁷ This class of medications help reduce hallucinations, delusions, and paranoia.

Additionally, antipsychotics help with mood changes associated with schizoaffective disorder. Second-generation antipsychotics are preferred over first-generation antipsychotics because of a better tolerability and adverse effect profile.

First-generation antipsychotics (typical antipsychotics)

• Haloperidol (Haldol)
• Fluphenazine (Prolixin)
• Chlorpromazine (Thorazine)
• Perphenazine (Trilafon)

Second-generation antipsychotics (atypical antipsychotics)

• Aripiprazole (Abilify)
• Quetiapine (Seroquel)
• Olanzapine (Zyprexa)
• Risperidone (Risperdal)
• Ziprasidone (Geodon)
• Lurasidone (Latuda)
• Asenapine (Saphris)
• Brexpiprazole (Rexulti)
• Cariprazine (Vraylar)
• Iloperidone (Fanapt)
• Clozapine (Clozaril, Versacloz)
• Paliperidone (Invega)
• Lumateperone (Caplyta)

In addition to oral formulations, some of the above medications are also available in long-acting acting injectables (LAIs). Most LAIs are once-monthly injections administered intramuscularly. However, there are some available to be administered less frequently, such as every 3 months or every 6 months. LAIs are appropriate for patients who have poor compliance to their antipsychotics and/or prefer less frequent administration of medications. Use of LAIs can reduce the pill burden of patients.

LAIs²

• Fluphenazine (Polixin): Dosing every 2 weeks.
• Haloperidol Econate (Haldol Deconate): Dosing every 4 weeks.
• Aripiprazole (Abilify Maintena, Aristada): Dosing every 4 weeks.
• Paliperidone Palmitate (Invega Sustena, Invega Trinza, Invega Hafyera): Dosing every 4 weeks, every 3 months, every 6 months, respectively.
• Risperidone (Risperdal Consta, Perseris): Dosing every 2 weeks, every 4 weeks, respectively.

Other than antipsychotics, patients with schizoaffective disorder may need additional medications to treat the mood component of the illness depending on the type of schizoaffective disorder. Patients are commonly prescribed mood stabilizers, such as valproic acid, and antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

Mood stabilizers

• Valproic acid (Depakote)
• Lithium (Lithobid, Eskalith)
• Lamotrigine (Lamictal)
• Carbamazepine (Tegretol)
• Oxcarbazepine (Trileptal)
• Topiramate (Topamax)

Antidepressants

• SSRIs
  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Paroxetine (Paxil)
  • Fluvoxamine (Luvox)
• SNRIs
  • Venlafaxine (Effexor)
  • Duloxetine (Cymbalta)
  • Vortioxetine (Trintellix)
  • Vilazodone (Viibryd)
  • Desvenlafaxine (Pristiq)
• Others
  • Mirtazapine (Remeron)
  • Bupropion (Wellbutrin)

In conclusion, both schizophrenia and schizoaffective disorder are chronic disabling mental disorders characterized by positive symptoms, such as hallucination, delusions, and paranoia. Schizoaffective disorder has additional mood symptoms, such as depression and bipolar symptoms.

Pharmacotherapy is the cornerstone of treatment for schizophrenia and schizoaffective disorder. The mainstay of treatment includes antipsychotics, mood stabilizers, and antidepressants. Treatment with antipsychotics can help to improve quality of life and social functioning.

References

1. Schizophrenia, 2022. National Institute of Mental Health (NIMH). 2022. Schizophrenia. [online] https://www.nimh.nih.gov/health/statistics/schizophrenia#:~:text=Across%20studies%20that%20use%20household,between%200.25%25%20and%200.64%25. Accessed 6 September 2022.
2. Schizophrenia, 2022. Who.int. 2022. Schizophrenia. [online]. https://www.who.int/news-room/fact-sheets/detail/schizophrenia#:~:text=Schizophrenia%20affects%20approximately%2024%20million,%25)%20among%20adults%20(2).Accessed 6 September 2022.
3. Schizophrenia - Symptoms and causes. Mayo Clinic. 2022. Schizophrenia - Symptoms and causes. [online] https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443. Accessed 6 September 2022.
4. Bowie CR, Harvey PD. Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr Dis Treat. 2006 Dec;2(4):531-6. doi: 10.2147/nedt.2006.2.4.531. PMID: 19412501; PMCID: PMC2671937.
5. Schizoaffective Disorder. NAMI: National Alliance on Mental Illness, 2022. Nami.org. 2022. Schizoaffective Disorder | NAMI: National Alliance on Mental Illness. [online]. https://www.nami.org/About-Mental-Illness/Mental-Health-Conditions/Schizoaffective-Disorder. Accessed 6 September 2022.
6. Schizoaffective disorder - Symptoms and causes, 2022. Mayo Clinic. 2022. Schizoaffective disorder - Symptoms and causes. [online] https://www.mayoclinic.org/diseases-conditions/schizoaffective-disorder/symptoms-causes/syc-20354504#:~:text=Schizoaffective%20disorder%20is%20a%20mental,such%20as%20depression%20or%20mania.Accessed 6 September 2022.
7. Keepers GA, Fochtmann LJ, Anzia JM, Benjamin S, Lyness JM, Mojtabai R, Servis M, Walaszek A, Buckley P, Lenzenweger MF, Young AS, Degenhardt A, Hong SH; (Systematic Review). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Am J Psychiatry. 2020 Sep 1;177(9):868-872. doi: 10.1176/appi.ajp.2020.177901. PMID: 32867516.