Clinical overview: updates in pharmacological options for the treatment of schizophrenia, bipolar disorder

Clinical overview: updates in pharmacological options for the treatment of schizophrenia, bipolar disorder

Schizophrenia is a mental condition in which reality is difficult to interpret. This may be due to multifaceted hallucinations or other behaviors that affect quality of life.

Credit: Olivier Le Moal –

Schizophrenia occurs in 1 in 300 people worldwide, with onset most commonly occurring in adolescence and persisting for life. There is no cure and it is usually treated with a first or second generation antipsychotic.

Xanomeline-trospium (Karxt) is a combination drug with a novel mechanism of action for the treatment of schizophrenia. Low levels of acetylcholine in the brain may theoretically have an impact on the sensory gating deficit and visual or auditory hallucinations associated with schizophrenia.

It is hypothesized that increasing available acetylcholine in the brain may alleviate the aforementioned symptoms. Xanomeline is an oral muscarinic cholinergic receptor agonist that stimulates the M1 and M4 muscarinic cholinergic receptors, known to impact the pathophysiology of schizophrenia.

Trospium is an oral panmuscarinic receptor antagonist whose structure prevents it from reaching the cerebrospinal fluid and, therefore, is not expected to cause adverse effects to the central nervous system (CNS). Using both together can stimulate brain muscarinic receptors with antipsychotic therapeutic doses of xanomeline while minimizing adverse events.

It would be the only drug approved to treat the negative symptoms of schizophrenia. The drugs currently used for schizophrenia are exclusively antipsychotics, and this new mechanism of action may impact patient outcomes.

Risperidone is an antipsychotic commonly used to treat schizophrenia. Rykindo (risperidone) is a new long-acting intramuscular (IM) formulation of this antipsychotic.

The ease of administration with an injection is advantageous because this patient population is commonly agitated and difficult to administer medications orally. The long duration (2 weeks) of efficacy with Rykindo will be beneficial in this population where compliance is often an issue.

There are other IM injections of antipsychotics and even another existing injection formulation of risperidone, such as Risperidal Consta (risperidone). Rykindo is a microsphere and, like Risperdal Consta, requires overlapping with oral risperidone while the IM takes effect.

Both are given every 2 weeks but Rykindo is unique because it only takes 7 days to see the effect compared to the 3 weeks required for Risperdal Consta. Perserisis the subcutaneous form (SQ), which does not require oral overlay, but is administered monthly.

Preference in available formulations will likely be patient specific. Rykindo is not only approved for adults with schizophrenia as monotherapy, but also as add-on therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults.

Lumateperone (Caplyta) is another recently approved agent for adults with schizophrenia and bipolar depression (I and II) as monotherapy and adjunctive therapy. Lumateperone acts on serotonin receptors like other second generation antipsychotics, alpha-2 agonists and SSRIs.

Unlike other antipsychotics, it has low affinity for the dopamine D2 receptor. Most antipsychotics have more than 60% occupancy at this receptor. Of these, quetiapine and cloazapine employment is closest to 60%; however, lumateperone has 39% occupancy.

This results in better tolerability with a lower rate of akathisia and extrapyramidal adverse events in both schizophrenia and bipolar disorder. Lumateperone is unique because it allows for the treatment of bipolar I and II depression as an adjunct or monotherapy.

Other agents of this class for the treatment of bipolar I and II disorder (quetiapine, lurasidone and cariprazine) can treat only in monotherapy. Lurasidone can do both monotherapy and adjunctive therapy, but only for bipolar I disorder.

Sublingual dexmedetomidine (Igalmi) was approved last year for acute agitation in adult patients with schizophrenia or bipolar I or II disorder. Keep an eye out for these drugs, as xanomeline-trospium will arrive in 2023 and lumateperone, Rykindo and Igalmi were approved by the FDA within the last year.


  1. Pharmacotherapy for schizophrenia: long-acting injectable antipsychotic drugs. . Updated. Accessed June 1, 2023.
  2. Major bipolar depression in adults: choice of treatment. . Updated. Accessed June 1, 2023. =2#.
  3. Schizophrenia. Mayo Clinic. January 7, 2020. Accessed June 1, 2023.
  4. What is Acetylcholine? American mental health. Accessed June 1, 2023.
  5. Schizophrenia. World Health Organization. Accessed June 1, 2023.
  6. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. New England Journal of Medicine. Accessed June 1, 2023.
  7. Dosage and administration of long-acting injectable antipsychotics for schizophrenia in adults. Updated. Accessed June 1, 2023. Caplyta Prescribing Information Highlights. FDA Approvals. (nd). Retrieved October 2, 2022 from
  8. For healthcare professionals – CAPLYTA (lumateperone) for bipolar depression. For healthcare professionals – CAPLYTA (lumateperone) for bipolar depression. (nd). Retrieved October 2, 2022 from
  9. BioXcel Therapeutics announces FDA approval of IGALMI (dexmedetomidine) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. BioXcel. Press release.

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