RESEARCH STARTER

Atypical antipsychotics (drug interactions)

Atypical antipsychotics, often referred to as second-generation antipsychotics, are primarily used to manage conditions such as schizophrenia, psychosis, mania, and severe depression. They include medications like olanzapine, risperidone, clozapine, quetiapine, and aripiprazole, among others. Understanding drug interactions with these medications is crucial for safe and effective treatment. Certain herbal supplements can lead to significant interactions; for example, St. John's wort may reduce the blood levels of atypical antipsychotics, potentially worsening psychotic symptoms or causing toxic side effects if the herb is discontinued. Glycine has shown some promise in enhancing the effects of certain antipsychotics, but its impact on all medications in this class remains uncertain. Preliminary evidence also suggests that ginkgo could help mitigate side effects and enhance the efficacy of these drugs, although it could pose risks like seizures in some patients. Other substances, such as chasteberry, ginseng, and kava, may either reduce the effectiveness of atypical antipsychotics or heighten side effects. Awareness of these interactions is essential for anyone considering or currently using atypical antipsychotics, ensuring both safety and optimal therapeutic outcomes.

Full Article

DEFINITION: Drug used to treat schizophrenia, psychosis, mania, depression, and agitation. Sometimes called second-generation antipsychotics.

  • INTERACTIONS: Ginkgo, glycine, St. John’s wort
  • DRUGS IN THIS FAMILY: Olanzapine (Zyprexa), risperidone (Risperdal), clozapine (Clozaril), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), paliperidone (Invega), lurasidone (Latuda), asenapine (Saphris), iloperidone (Fanapt)

St. John’s Wort

Effect: Possible Harmful Interaction

The herb St. John’s wort might reduce levels of these medications in the blood. This could lead to an increase in the severity of psychotic symptoms.

Perhaps even more dangerously, if medication levels are adjusted for an individual already taking St. John’s wort, stopping the herb could cause these levels to rise, potentially causing dangerous toxic symptoms. Additionally, St. John's wort worsens psychotic symptoms for some individuals, typically those with schizophrenia or bipolar disorder diagnoses.

Glycine

Effect: Possible Benefits and Risks

A few studies suggest that the amino acid glycine may augment the action of phenothiazine antipsychotic drugs. It might also augment the action of olanzapine and risperidone, but whether it augments or decreases the effectiveness of clozapine remains unclear.

Ginkgo

Effect: Possible Helpful Interaction

Preliminary evidence suggests that ginkgo might reduce the side effects and increase the efficacy of various antipsychotic medications, including atypical antipsychotic drugs. This may cause seizures in some patients.

Though rare, men taking risperidone (Risperdal) may experience priapism—an erection lasting more than four hours.

Other interactions

Chasteberry, often taken for menopause or infertility, may make some atypical antipsychotics less effective. Ginseng and kava may make these drugs more effective and increase the chances of side effects, particularly when taken with chlorpromazine (Thorazine).


Bibliography

Buchanan, R. W., et al. “The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): The Efficacy of Glutamatergic Agents for Negative Symptoms and Cognitive Impairments.” American Journal of Psychotherapy, vol. 164, 2007, pp. 1593-1602.

De Smet, P. A., and D. J. Touw. “Safety of St. John’s Wort.” The Lancet, vol. 355, 2000, pp. 575-76.

Diaz, P., et al. “Double-Blind, Placebo-Controlled, Crossover Trial of Clozapine Plus Glycine in Refractory Schizophrenia Negative Results.” Journal of Clinical Psychopharmacology, vol. 25, 2005, pp. 277-78.

Evins, A. E., et al. “Placebo-Controlled Trial of Glycine Added to Clozapine in Schizophrenia.” American Journal of Psychiatry, vol. 157, 2000, pp. 826-28.

Heresco-Levy, U., et al. “High-Dose Glycine Added to Olanzapine and Risperidone for the Treatment of Schizophrenia.” Biological Psychiatry, vol. 55, 2004, pp. 165-71.

Kennedy, William K., et al. “Clinically Significant Drug Interactions with Atypical Antipsychotics.” CNS Drugs, vol. 27, 2013, pp. 1021-48, doi:10.1007/s40263-013-0114-6. Accessed 15 Dec. 2025.

Meltzer, Herbert Y., and Erick Gadaleta. "Contrasting Typical and Atypical Antipsychotic Drugs." Focus, vol. 19, no. 1, 2021, pp. 3-13. Psychiatry Online, doi.org/10.1176/appi.focus.20200051. Accessed 15 Dec. 2025.

Potkin, S. G., et al. “Effect of Clozapine and Adjunctive High-Dose Glycine in Treatment-Resistant Schizophrenia.” American Journal of Psychiatry, vol. 156, 1999, pp. 145-47.

Preston, Claire L. Stockley’s Drug Interactions. 12th ed., Pharmaceutical Press, 2021.

Spina, Edoardo, et al. "Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents." Pharmaceuticals, vol. 13, no. 12, 2020. MDPI, doi.org/10.3390/ph13120439. Accessed 15 Dec. 2025.

Willner, Keith, et al. "Atypical Antipsychotic Agents - StatPearsl." National Center for Biotechnology Information, 1 May 2024, www.ncbi.nlm.nih.gov/books/NBK448156. Accessed 15 Dec. 2025.

Full Article

DEFINITION: Drug used to treat schizophrenia, psychosis, mania, depression, and agitation. Sometimes called second-generation antipsychotics.

  • INTERACTIONS: Ginkgo, glycine, St. John’s wort
  • DRUGS IN THIS FAMILY: Olanzapine (Zyprexa), risperidone (Risperdal), clozapine (Clozaril), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), paliperidone (Invega), lurasidone (Latuda), asenapine (Saphris), iloperidone (Fanapt)

St. John’s Wort

Effect: Possible Harmful Interaction

The herb St. John’s wort might reduce levels of these medications in the blood. This could lead to an increase in the severity of psychotic symptoms.

Perhaps even more dangerously, if medication levels are adjusted for an individual already taking St. John’s wort, stopping the herb could cause these levels to rise, potentially causing dangerous toxic symptoms. Additionally, St. John's wort worsens psychotic symptoms for some individuals, typically those with schizophrenia or bipolar disorder diagnoses.

Glycine

Effect: Possible Benefits and Risks

A few studies suggest that the amino acid glycine may augment the action of phenothiazine antipsychotic drugs. It might also augment the action of olanzapine and risperidone, but whether it augments or decreases the effectiveness of clozapine remains unclear.

Ginkgo

Effect: Possible Helpful Interaction

Preliminary evidence suggests that ginkgo might reduce the side effects and increase the efficacy of various antipsychotic medications, including atypical antipsychotic drugs. This may cause seizures in some patients.

Though rare, men taking risperidone (Risperdal) may experience priapism—an erection lasting more than four hours.

Other interactions

Chasteberry, often taken for menopause or infertility, may make some atypical antipsychotics less effective. Ginseng and kava may make these drugs more effective and increase the chances of side effects, particularly when taken with chlorpromazine (Thorazine).


Bibliography

Buchanan, R. W., et al. “The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): The Efficacy of Glutamatergic Agents for Negative Symptoms and Cognitive Impairments.” American Journal of Psychotherapy, vol. 164, 2007, pp. 1593-1602.

De Smet, P. A., and D. J. Touw. “Safety of St. John’s Wort.” The Lancet, vol. 355, 2000, pp. 575-76.

Diaz, P., et al. “Double-Blind, Placebo-Controlled, Crossover Trial of Clozapine Plus Glycine in Refractory Schizophrenia Negative Results.” Journal of Clinical Psychopharmacology, vol. 25, 2005, pp. 277-78.

Evins, A. E., et al. “Placebo-Controlled Trial of Glycine Added to Clozapine in Schizophrenia.” American Journal of Psychiatry, vol. 157, 2000, pp. 826-28.

Heresco-Levy, U., et al. “High-Dose Glycine Added to Olanzapine and Risperidone for the Treatment of Schizophrenia.” Biological Psychiatry, vol. 55, 2004, pp. 165-71.

Kennedy, William K., et al. “Clinically Significant Drug Interactions with Atypical Antipsychotics.” CNS Drugs, vol. 27, 2013, pp. 1021-48, doi:10.1007/s40263-013-0114-6. Accessed 15 Dec. 2025.

Meltzer, Herbert Y., and Erick Gadaleta. "Contrasting Typical and Atypical Antipsychotic Drugs." Focus, vol. 19, no. 1, 2021, pp. 3-13. Psychiatry Online, doi.org/10.1176/appi.focus.20200051. Accessed 15 Dec. 2025.

Potkin, S. G., et al. “Effect of Clozapine and Adjunctive High-Dose Glycine in Treatment-Resistant Schizophrenia.” American Journal of Psychiatry, vol. 156, 1999, pp. 145-47.

Preston, Claire L. Stockley’s Drug Interactions. 12th ed., Pharmaceutical Press, 2021.

Spina, Edoardo, et al. "Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents." Pharmaceuticals, vol. 13, no. 12, 2020. MDPI, doi.org/10.3390/ph13120439. Accessed 15 Dec. 2025.

Willner, Keith, et al. "Atypical Antipsychotic Agents - StatPearsl." National Center for Biotechnology Information, 1 May 2024, www.ncbi.nlm.nih.gov/books/NBK448156. Accessed 15 Dec. 2025.

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