Skip to main content Accessibility help
Hostname: page-component-56f9d74cfd-dpvgk Total loading time: 0.651 Render date: 2022-06-26T00:21:16.879Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

Book contents


Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer
University of California, San Diego
Stephen M. Stahl
University of California, Riverside and San Diego
Get access


Antipsychotics have numerous evidence-based uses in the twenty-first century, including schizophrenia spectrum and other psychotic disorders, bipolar disorder, unipolar major depression, behavioral disturbances of autism, tic disorders, and obsessive compulsive disorder [1]. The application of antipsychotic therapy in many of these conditions is adjunctive, and it may be withdrawn during less active phases of the illness. For patients with schizophrenia spectrum disorders, antipsychotics are the foundation of treatment without which the patient is at risk for relapse, and the attendant psychiatric, social, and legal consequences [2, 3]. Given the level of disability often encountered with the onset of illness, the care and management of individuals with schizophrenia exerts a significant economic toll on society [4–6]; moreover, this burden accrues most directly to families and direct caregivers in the form of financial loss compounded by stress and decreased quality of life [7, 8]. Of particular concern are the disproportionate direct and indirect costs associated with treatment-resistant schizophrenia (TRS) [4] (see Figure 0.1).

Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Meyer, J. M. (2018). Pharmacotherapy of psychosis and mania. In Brunton, L. L., Hilal-Dandan, R., and Knollmann, B. C., eds.,Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edn. Chicago, IL: McGraw-Hill, pp. 279302.Google Scholar
Rezansoff, S. N., Moniruzzaman, A., Fazel, S., et al. (2017). Adherence to antipsychotic medication and criminal recidivism in a Canadian provincial offender population. Schizophr Bull, 43, 10021010.CrossRefGoogle Scholar
Takeuchi, H., Siu, C., Remington, G., et al. (2019). Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology, 44, 10361042.CrossRefGoogle ScholarPubMed
Kennedy, J. L., Altar, C. A., Taylor, D. L., et al. (2014). The social and economic burden of treatment-resistant schizophrenia: A systematic literature review. Int Clin Psychopharmacol, 29, 6376.CrossRefGoogle ScholarPubMed
Cloutier, M., Aigbogun, M. S., Guerin, A., et al. (2016). The economic burden of schizophrenia in the United States in 2013. J Clin Psychiatry, 77, 764771.CrossRefGoogle ScholarPubMed
Charlson, F. J., Ferrari, A. J., Santomauro, D. F., et al. (2018). Global epidemiology and burden of schizophrenia: Findings from the Global Burden of Disease Study 2016. Schizophr Bull, 44, 11951203.CrossRefGoogle ScholarPubMed
Nuttall, A. K., Thakkar, K. N., Luo, X., et al. (2019). Longitudinal associations of family burden and patient quality of life in the context of first-episode schizophrenia in the RAISE-ETP study. Psychiatry Res, 276, 6068.CrossRefGoogle ScholarPubMed
Wan, K. F. and Wong, M. M. C. (2019). Stress and burden faced by family caregivers of people with schizophrenia and early psychosis in Hong Kong. Intern Med J, 49 Suppl 1, 915.CrossRefGoogle ScholarPubMed
McCutcheon, R., Beck, K., Bloomfield, M. A., et al. (2015). Treatment resistant or resistant to treatment? Antipsychotic plasma levels in patients with poorly controlled psychotic symptoms. J Psychopharmacol, 29, 892897.CrossRefGoogle ScholarPubMed
McCutcheon, R., Beck, K., D’Ambrosio, E., et al. (2018). Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatr Scand, 137, 3946.CrossRefGoogle Scholar
Dufort, A. and Zipursky, R. B. (2019). Understanding and managing treatment adherence in schizophrenia. Clin Schizophr Relat Psychoses, Scholar
Byerly, M. J., Thompson, A., Carmody, T., et al. (2007). Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia. Psychiatr Serv, 58, 844847.CrossRefGoogle Scholar
Brain, C., Sameby, B., Allerby, K., et al. (2014). Twelve months of electronic monitoring (MEMS) in the Swedish COAST-study: A comparison of methods for the measurement of adherence in schizophrenia. Eur Neuropsychopharmacol, 24, 215222.CrossRefGoogle Scholar
Lopez, V. L., Shaikh, A., Merson, J., et al. (2017). Accuracy of clinician assessments of medication status in the emergency setting – a comparison of clinician assessment of antipsychotic usage and plasma level determination. J Clin Psychopharmocol, 37, 310314.CrossRefGoogle ScholarPubMed
Correll, C. U., Jain, R., Meyer, J. M., et al. (2019). Relationship between the timing of relapse and plasma drug levels following discontinuation of cariprazine treatment in patients with schizophrenia: indirect comparison with other second-generation antipsychotics after treatment discontinuation. Neuropsychiatr Dis Treat, 15, 25372550.CrossRefGoogle ScholarPubMed
Veselinovic, T., Scharpenberg, M., Heinze, M., et al. (2019). Dopamine D2 receptor occupancy estimated from plasma concentrations of four different antipsychotics and the subjective experience of physical and mental well-being in schizophrenia: Results from the randomized NeSSy Trial. J Clin Psychopharmacol, 39, 550560.CrossRefGoogle ScholarPubMed
Schoretsanitis, G., Kane, J. M., Correll, C. U., et al. (2020). Blood levels to optimize antipsychotic treatment in clinical practice: A joint consensus statement of the American Society of Clinical Psychopharmacology (ASCP) and the Therapeutic Drug Monitoring (TDM) Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). J Clin Psychiatry, 81, Scholar
Best-Shaw, L., Gudbrandsen, M., Nagar, J., et al. (2014). Psychiatrists’ perspectives on antipsychotic dose and the role of plasma concentration therapeutic drug monitoring. Ther Drug Monit, 36, 486493.CrossRefGoogle ScholarPubMed
Renton, C. A., Affleck, J. W., Carstairs, G. M., et al. (1963). A follow-up of schizophrenic patients in Edinburgh. Acta Psychiatr Scand, 39, 548600.CrossRefGoogle ScholarPubMed
Willcox, D. R., Gillan, R., and Hare, E. H. (1965). Do psychiatric out-patients take their drugs? BMJ, 2, 790792.CrossRefGoogle Scholar
Remington, G., Teo, C., Mann, S., et al. (2013). Examining levels of antipsychotic adherence to better understand nonadherence. J Clin Psychopharmacol, 33, 261263.CrossRefGoogle ScholarPubMed
Velligan, D. I., Wang, M., Diamond, P., et al. (2007). Relationships among subjective and objective measures of adherence to oral antipsychotic medications. Psychiatr Serv, 58, 11871192.CrossRefGoogle ScholarPubMed
Rostami-Hodjegan, A., Amin, A. M., Spencer, E. P., et al. (2004). Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: A predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol, 24, 7078.CrossRefGoogle ScholarPubMed
Van Putten, T., Marder, S. R., Wirshing, W. C., et al. (1991). Neuroleptic plasma levels. Schizophr Bull, 17, 197216.CrossRefGoogle ScholarPubMed
Wei, F. C., Jann, M. W., Lin, H. N., et al. (1996). A practical loading dose method for converting schizophrenic patients from oral to depot haloperidol therapy. J Clin Psychiatry, 57, 298302.Google ScholarPubMed
Hiemke, C., Bergemann, N., Clement, H. W., et al. (2018). Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: Update 2017. Pharmacopsychiatry, 51, 962.Google ScholarPubMed
Lopez, L. V. and Kane, J. M. (2013). Plasma levels of second-generation antipsychotics and clinical response in acute psychosis: A review of the literature. Schizophr Res, 147, 368374.CrossRefGoogle ScholarPubMed
Meyer, J. M. and Stahl, S. M. (2019). The Clozapine Handbook. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
Baumann, P., Hiemke, C., Ulrich, S., et al. (2004). The AGNP-TDM expert group consensus guidelines: Therapeutic drug monitoring in psychiatry. Pharmacopsychiatry, 37, 243265.CrossRefGoogle Scholar
Hiemke, C., Baumann, P., Bergemann, N., et al. (2011). AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry, 44, 195235.Google ScholarPubMed
Muller, M. J., Regenbogen, B., Hartter, S., et al. (2007). Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia. J Psychiatr Res, 41, 673679.CrossRefGoogle ScholarPubMed
Marder, S. R. and Meibach, R. C. (1994). Risperidone in the treatment of schizophrenia. Am J Psychiatry, 151, 825835.Google ScholarPubMed
Kelly, D. L., Richardson, C. M., Yang, Y., et al. (2006). Plasma concentrations of high-dose olanzapine in a double-blind crossover study. Hum Psychopharmacol, 21, 393398.CrossRefGoogle Scholar
Simpson, G. M. and Kunz-Bartholini, E. (1968). Relationship of individual tolerance, behavior and phenothiazine produced extrapyramidal system disturbance. Dis Nerv System, 29, 269274.Google ScholarPubMed
Meyer, J. M. (2014). A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: case vignettes. CNS Spectr, 19, 432438.CrossRefGoogle ScholarPubMed
Meyer, J. M. (2020). Monitoring and improving antipsychotic adherence in outpatient forensic diversion programs. CNS Spectr, 25, 136144.CrossRefGoogle ScholarPubMed
Law, S., Haddad, P. M., Chaudhry, I. B., et al. (2015). Antipsychotic therapeutic drug monitoring: psychiatrists’ attitudes and factors predicting likely future use. Ther Adv Psychopharmacol, 5, 214223.CrossRefGoogle ScholarPubMed
Vos, T., Abajobir, A. A., Abbafati, C., et al. (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet, 390, 12111259.CrossRefGoogle Scholar
Moreno-Kustner, B., Martin, C., and Pastor, L. (2018). Prevalence of psychotic disorders and its association with methodological issues: A systematic review and meta-analyses. PLoS One, 13, e0195687.CrossRefGoogle ScholarPubMed
Chong, H. Y., Teoh, S. L., Wu, D. B., et al. (2016). Global economic burden of schizophrenia: a systematic review. Neuropsychiatr Dis Treat, 12, 357373.Google ScholarPubMed
Predmore, Z., Mattke, S., and Horvitz-Lennon, M. (2015). Improving antipsychotic adherence among patients with schizophrenia: savings for states. Psychiatr Serv, 66, 343345.CrossRefGoogle ScholarPubMed
Predmore, Z., Mattke, S., and Horvitz-Lennon, M. (2018). Potential benefits to patients and payers from increased measurement of antipsychotic plasma levels in the management of schizophrenia. Psychiatr Serv, 69, 1214.CrossRefGoogle ScholarPubMed
Green, B., Korell, J., Remmerie, B., et al. (2017). Optimizing antipsychotic patient management using population pharmacokinetic models and point-of-care testing. CPT Pharmacometrics Syst Pharmacol, 6, 573575.CrossRefGoogle ScholarPubMed
Kelly, D., Glassman, M., Mackowick, M., et al. (2020). O9.1. Satisfaction with using a novel fingerstick for absolute neutrophil count (ANC) at the point of treatment in patients treated with clozapine. Schizophr Bull, 46, S20S21.CrossRefGoogle Scholar
Maxfield, K. and Zineh, I. (2021). Precision dosing: a clinical and public health imperative. JAMA, doi: 10.1001/jama.2021.1004. Online ahead of print.CrossRefGoogle Scholar
Passos, I. C., Ballester, P., Rabelo-da-Ponte, F. D., et al. (2021). Precision psychiatry: the future is now. Can J Psychiatry, 24, doi: 10.1177/0706743721998044.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats