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Highlights from an observational study on long-acting injectables (LAI) for the treatment of schizophrenia were presented at the 2021 American Psychiatric Association (APA) Annual Meeting in a poster titled, 

Healthcare Resource Utilization and Costs Pre-/Post-Long-Acting Injectable Antipsychotic Initiation in Commercially Insured Young Adults with Schizophrenia

This presentation focused on several key points. Most notably, the rate of relapse significantly decreased following treatment initiation of LAI for young adults aged 18 to 35 diagnosed with schizophrenia. Additionally, costs were reduced across the board; all-cause total medical costs, mental health-related total costs, and total schizophrenia-related costs were all decreased.

“The study results showed that LAI treatment for young adults with schizophrenia may be associated with significant cost savings to commercial payers,” according to the Janssen Pharmaceuticals poster.

Janssen also presented a poster looking at the 

Changes in Behavioral Healthcare Service Use Among Patients With Schizophrenia Associated With COVID-19 Pandemic.

This poster demonstrated substantial increases in telehealth, and a decrease in partial day hospitalizations and visits to community mental health centers during the COVID-19 pandemic among adult patients with schizophrenia. According to the study, 69.1% of psychiatry encounters were delivered via telehealth by June of 2020.




Both Janssen’s poster presentations demonstrated potential benefits for adult patients living with schizophrenia in terms of not only accessibility of psychiatric care, but also potential cost-saving benefits for patients.

1. Fu AZ, Pesa JA, Lakey S, Benson C. Healthcare resource utilization and costs pre-/post-long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia. Janssen Scientific Affairs. 

http://www.apothecom.com/review/qrcodes/150109058/APA_PALM-OUT-585_206_Poster.jpg

2. Liberman JN, Pesa J, Petrillo M, Ruetsch C. Changes in behavioral healthcare service use among patients with schizophrenia associated with COVID-19 pandemic. Health Analytics, Janssen Scientific Affairs. 

http://apothecom.com/review/qrcodes/150109057/APA_PHR-OUT-947_Poster.jpg

Two posters presented at the APA virtual meeting demonstrated long-acting injectable positive results, costs savings, and increased telehealth for patients with schizophrenia. 

Posters Indicate Potential Benefit for Patients With Schizophrenia

Sunovion Pharmaceuticals presented data on the late-stage pipeline candidate SEP-363856, a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT

 agonist activity under investigation for the treatment of schizophrenia at the 2021 American Psychiatric Association Virtual Annual Meeting.

“The SEP-363856 safety analysis presented at APA supports previous clinical trial evidence that this agent is associated with a differentiated side effect profile compared to currently approved atypical antipsychotics. These data further support the characterization of SEP-363856 as representing a new class of medicines for the treatment of schizophrenia,” Armin Szegedi, MD, PhD, Senior Vice President and Chief Medical Officer of Sunovion, said to the press. “We are pleased to discuss these SEP-363856 data with the clinical community to foster further understanding of this novel compound.”

SEP-363856 was highlighted in the poster titled “The Safety Profile of the TAAR1 Agonist, SEP-363856, is Distinct From Atypical Antipsychotics,” (poster P12-007). The poster covered data analysis from the US Food and Drug Administration’s (FDA) real-world adverse event reporting database (FAERS), and compared the frequency of adverse events (AEs) related to antipsychotic schizophrenia treatment occurring in 11 atypical antipsychotics to those in observed with SEP-363856 in clinical studies.

The analysis found the cumulative rate and patterns of AEs was distinctly different for SEP-363856 than for atypical antipsychotics.

The presentation “Effects of SEP-363856, a Novel TAAR1 Agonist, on Negative Symptoms in Schizophrenia: Results Across an Initial Double-Blind Acute Study and a 6-Month, Open-Label Extension Study,” (poster P11-086), also highlighted the pipeline candidate. It demonstrated that short-term treatment with SEP-363856 saw improvement in negative symptoms of schizophrenia when compared to placebo. Long-term treatment also saw additional mean improvement in the Brief Negative Symptom Scale (BNSS) total score and BNSS factor scores.

1. Sunovion. Sunovion presents data from marketed and late-stage development psychiatric compounds at the American Psychiatric Association (APA) Annual Meeting 2021. News release. May 3, 2021. 

https://news.sunovion.com/press-releases/press-releases-details/2021/Sunovion-Presents-Data-From-Marketed-and-Late-Stage-Development-Psychiatric-Compounds-At-The-American-Psychiatric-Association-APA-Annual-Meeting-2021/default.aspx

Data presented at the 2021 APA Virtual Annual Meeting show promise for treating schizophrenia.  

Late-Stage Pipeline Candidate Looks Promising for the Treatment of Schizophrenia 

It has been said that individuals avoid discussing religion, politics, and money. In this article, we will address another taboo topic: sexual dysfunction (SD), which occurs when an individual has difficulty with 1 or more components of the 

, presenting as decreased libido, early or delayed ejaculation, orgasmic dysfunction, impaired genital sensation, erectile dysfunction, and/or insufficient lubrication in women.

SD is relatively common. In the general adult population, the estimated prevalence of SD is 20% to 30% in men and 40% to 45% in women.

 Certain risk factors may increase the risk, including psychiatric disease. For example, based on International Classification of Diseases, Tenth Revision (ICD-10) definitions, 74% of men and 82% of women with schizophrenia, reported at least 1 sexual problem.

 However, psychiatric patients experiencing SD are often hesitant to disclose concerns to health care professionals.

Medicinal treatment of psychiatric diseases is also a significant cause of SD. Antidepressants, antipsychotics, and benzodiazepines are 3 drug classes that are potent etiologies of SD (

 According to a validated survey for assessing SD (SalSex), nearly 

 treated for a psychotic disorder developed SD.

 Another study suggested that 25% to 80% of patients treated with antidepressants developed SD.

 This is a major concern, as some patients have shown poor tolerance to the sexual side effects of psychiatric medications and have considered treatment cessation as a result.

 that the sexual side effects of psychiatric medications persist even after medication discontinuation, causing patients great distress.

SD is a significant concern for patients on psychiatric medications. However, SD is often inadequately addressed.

Medication Classes and Sexual Dysfunction

 Selective serotonin reuptake inhibitors (SSRIs) are commonly utilized in the treatment of major depression, anxiety disorders, posttraumatic stress disorder, and obsessive-compulsive disorder, among others.

 The prevalence of sexual side effects is not well defined. One post-market study estimated SD prevalence in patients treated with SSRIs between 5% and 15%,

 while some studies reported up to 80% of patients experienced sexual side effects.

 Although some patients experiencing sexual side effects may see their symptoms resolve over the course of treatment, the vast majority will continue to experience side effects during SSRI treatment.

 Some patients may continue to suffer from persistent side effects despite the discontinuing medication, a condition known as post-SSRI sexual dysfunction (PSSD).

 Although there is limited clinical trial data, available studies found the highest incidence of sexual side effects in patients treated with paroxetine, followed by fluvoxamine, sertraline, and fluoxetine.

A proposed mechanism for SSRI-induced SD lies within the interaction between serotonin and 5-hydroxytryptamine receptors (5HT1A).

 SSRIs are hypothesized to cause downregulation of 5HT1A due to the persistent stimulation by serotonin and resulting epigenetic changes that have implications for regulation of sexual motivation. It is likely that other 5HT receptor subtypes are similarly affected. The effect of elevated serotonin on levels of other hormones and neurotransmitters that play an important role in sexual function, such as testosterone and dopamine, may also account for some of SSRIs’ sexual side effects. These effects appear to be dose-dependent, with higher doses increasing one’s risk of SD.

 Thus, providers must weigh the potential benefits of increasing drug doses with increasing risk of adverse effects.

 SD is a common adverse effect (present in up to 48% to 75% of patients) of both oral and depotantipsychotic medications.

 Results of a recent meta-analysis described SD prevalence in those treated with oral 

 Treatment with quetiapine (16%), ziprasidone (18%), and aripiprazole (27%) were associated with the lowest rates of SD. Olanzapine (40%), risperidone (43%), haloperidol (45%), clozapine (52%), and thioridazine (60%) were associated with higher prevalence of SD. In long-acting depot antipsychotics, first- versus second-generation antipsychotics are more strongly associated with SD.

Sexual side effects can likely be traced to the disruption of various neurogenic and hormonal factors impacted by the antipsychotics.

 Mechanisms vary based on action of specific medications. For instance, antidopaminergic medications likely impact the dopaminergic activity of the mesolimbic system, which is integral to sexual functioning. Atypical antipsychotics that target postsynaptic 5HT receptors can negatively affect arousal, orgasm, and ejaculation, as serotonin inhibits sexual desire. Medications that influence levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, or other neuroendocrine changes can lead to imbalance of these factors necessary for optimal sexual functioning. This was illustrated in the meta-analysis described previously, which generally showed prolactin-raising antipsychotics (eg, haloperidol) caused greater SD compared with prolactin-sparing drugs (eg, ziprasidone).

 Also, as with SSRIs, antipsychotic-based SD appears to be dose-related.

Thus, to assess a patient’s risk of SD, providers must consider both the dosage and mechanism of a particular antipsychotic.

 Benzodiazepines have been reported to result in SD, but this effect is less evident and less reported than the classes of drugs previously discussed. The 

 of a multicenter double-blind randomized comparative study of patients treated with acute phase alprazolam for panic disorder found that the benzodiazepines did not cause SD.

 Other studies point to increased sexual arousal because of reduced anxiety in patients treated with benzodiazepines.

 in 25% to 50% of patient samples treated with alprazolam.

 It is possible that benzodiazepines may reduce anxiety-related aspects of SD while causing anorgasmia and/or other negative impacts on sexual function.

Although there is limited evidence of the mechanism behind the SD caused by benzodiazepines, contributing factors could include effects on 

 and drug-drug interactions. Benzodiazepines are allosteric modulators of the gamma-amino butyric acid (GABA)-A receptor.

 GABA, a central nervous system neurotransmitter, has been associated with decreased sexual behavior. Increased GABA activity could account for decreased sexual function. Benzodiazepines may also contribute indirectly to SD through increased concentrations of concurrently taken medications because of interactions with the cytochrome P450 system.

Mental health care professionals should take the lead in discussing SD with patients. Patients are often unable or unwilling to initiate a dialogue about sexual concerns, and SD could go unnoticed. For example, 1 study showed that 63% of patients experiencing sexual side effects from treatment but did not spontaneously report the issue.

 Importantly, 1 of 3 of those patients felt their dysfunction was significantly impacting their quality of life. An additional study revealed that 50% of patients rarely if ever discussed their SD with providers, even if it had affected adherence to treatment.

The sexual effects of psychiatric medications should be communicated at 3 distinct times: before, during, and after treatment. It is often difficult to discern retroactively if a patient’s SD is from their mental health condition or their psychiatric medications. Thus, establishing a baseline level of sexual function before treatment is extremely helpful. Then, throughout treatment, the clinician should continuously follow up with patients on their sexual function either verbally or through the usage of validated questionnaires.

If a patient is experiencing treatment-related dysfunction, it is important to ask how distressed the patient is by their SD.

 Not all patients with treatment-induced SD are greatly concerned about it.

 It may also be helpful to directly ask patients if their SD has ever caused them to cease their medications.

Finally, if patients complete treatment, it is important to follow up and inquire if their SD has resolved, as some patients experience lingering SD after discontinuation of treatment.

 It is therefore important to detect this and help patients seek appropriate therapies to treat their SD.

Irrespective of the presumed cause of SD, the initial management of patients presenting with SD symptoms must begin with a thorough history and physical exam to 

 that the SD is indeed a product of psychiatric medication use (

 The clinician should also utilize validated psychometric questionnaires, such as the International Index of Erectile Function (IIEF) or its short version, the Sexual Health Inventory for Men (SHIM) (

),at the initial and follow-up visits to assess the various sexual function domains (ie, erectile function, libido, orgasmic function, intercourse, overall satisfaction) at 

 and following initiation or modification of a specific treatment modality.

 Identifying reversible risk factors for SD, such as hypogonadism, hypertension, and obesity, and initiating appropriate treatment should be the clinician’s primary focus during the initial evaluation.

 It is only after addressing easily reversible risk factors for SD that a clinician should suspect psychotropic medications as the cause of SD, especially if the timing of SD remains unclear.

Given the lack of evidence-based treatments, management of patients with presumed psychotropic-induced SD proves to be more of an art rather than a science, and only 20% of prescribers discuss this topic with their patients.

 For the most part, management strategies include a wait and see approach, reduction in medication dosage, switching medications, adjunct medications, cognitive behavioral therapy (CBT), and behavioral modifications (see the following subsections) (

 Regardless of which management strategy a clinician employs, treatment should always follow an individualized, patient-centered approach, focusing primarily on minimizing SD without compromising the psychiatric well-being of the patient.

 Clinicians must also determine what strategies their patients have already tried to identify which treatments are more likely to be effective.

 Specifically regarding SSRI use, clinicians must educate their patients about the risks of PSSD.

 Although various management options for PSSD have been proposed, none have proven effective and there remains no definitive treatment.

A wait and see approach may prove beneficial for some patients, as side effects from medications, particularly SSRIs, can dissipate over time. One study suggested that SD remits in 6 months for approximately 80% of patients, while others report remission in only 10%.

 Another approach involves reduction in dosage, if feasible. SD related to antidepressants may be a dose-dependent adverse effect; therefore, reduction of dosage to a minimum effective dose may be beneficial. However, reduction in dosage could compromise the patient’s mental health, and depending on the particular medication, improvement in sexual function may take several months, which makes this strategy inappropriate for some patients.

 Moreover, many patients only require short-term courses of antidepressants, so in the appropriate setting, cessation of the medication altogether could be the best option.

 Although there is some evidence supporting the use of drug holidays (ie, temporarily discontinuing the drug on weekends), this may lead to withdrawal symptoms or medication nonadherence and is not recommended.

 Another strategy involves switching medications, in particular from an SSRI to a non-SSRI antidepressant. This may allow for the continuation of psychiatric treatment while potentially improving sexual function and adherence. For instance, switching to bupropion, an antidepressant with a favorable sexual side effect profile, has been used with success in patients with previous SSRI-induced SD,

 although these medications have their own unique set of side effects which, in some situations, may be even more distressing to the patient.

 Augmentation strategies consisting of adding another pharmacological or psychotherapeutic treatment to counteract the psychotropic-related SD have shown success in some patients. Addition of bupropion, tamsulosin, phosphodiesterase-5 inhibitors (eg, sildenafil), testosterone, and 5-HT2 antagonists (eg, mirtazapine) to counteract SD without SSRI cessation can be an effective 

 CBT, sex therapy, couples counseling, acupuncture, and behavioral modifications such as the use of vibrators and scheduled sexual activity (ie, in the morning before the daily SSRI dose) have demonstrated mixed benefit.

SD from psychiatric medications is relatively common. If a patient develops SD, multiple treatment strategies exist to help alleviate it. However, SD cannot be treated until it is first identified. Early, continuous, and direct conversations with patients about their sexual function is necessary—and should be anything but taboo.

is a medical student at Tulane University School of Medicine (TUSOM) pursuing urology. 

is a professor of urology and chief of the section of andrology at TUSOM. The authors note they have nothing to disclose regarding this article.

1. Lewis RW, Fugl-Meyer KS, Corona G, et al. 

Definitions/epidemiology/risk factors for sexual dysfunction

2. Harley EW, Boardman J, Craig T. Sexual problems in schizophrenia: prevalence and characteristics. A cross sectional survey. 

3. Montejo AL, Majadas S, Rico-Villademoros F, et al. 

Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics

4. Bahrick AS. Post SSRI sexual dysfunction. 

5. Atmaca M. Selective serotonin reuptake inhibitor-induced sexual dysfunction: current management perspectives. 

6. Stahl SM. Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. 

7. Hirschfeld RM. Long-term side effects of SSRIs: sexual dysfunction and weight gain. 

8. Allen K, Baban A, Munjiza J, Pappa S. Management of antipsychotic-related sexual dysfunction: systematic review. 

9. Montejo AL, de Alarcón R, Prieto N, et al. 

Management strategies for antipsychotic-related sexual dysfunction: a clinical approach

10. Kaufman KR, Coluccio M, Linke M, et al. Alprazolam-induced dose-dependent anorgasmia: case analysis. 

11. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. 

12. Lambert M, Conus P, Eide P, et al. Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence. 

Post-SSRI sexual dysfunction: a literature review

14. Rappek NAM, Sidi H, Kumar J, et al. Serotonin selective reuptake inhibitors (SSRIs) and female sexual dysfunction (FSD): hypothesis on its association and options of treatment. 

15. Safer DJ. Raising the minimum effective dose of serotonin reuptake inhibitor antidepressants: adverse drug events. 

16. Plevin D, Galletly C, Roughan P. Sexual dysfunction in men treated with depot antipsychotic drugs: a pilot study.

17. Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. 

18. Park EJ, Amatya S, Kim MS, et al. Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia. 

19. Novick D, Haro JM, Perrin E, Suarez D, et al. Tolerability of outpatient antipsychotic treatment: 36-month results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. 

20. Bobes J, Garc A-Portilla MP, Rejas J, et al. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study. 

Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders

22. Fava M, Borofsky GF. Sexual disinhibition during treatment with a benzodiazepine: a case report. 

23. Rosenberg KP, Bleiberg KL, Koscis J, Gross C. A survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. 

24. Rizvi SJ, Yeung NW, Kennedy SH. Instruments to measure sexual dysfunction in community and psychiatric populations. 

25. Lorenz T, Rullo J, Faubion S. Antidepressant-induced female sexual dysfunction. 

26. Shindel A, Althof S, Carrier S, et al. Disorders of ejaculation: an AUA/SMSNA guideline. American Urological Association Website. Accessed Jan 28, 2021. 

https://www.auanet.org/guidelines/disorders-of-ejaculation

27. Hatzimouratidis K, Giuliano F, Moncada I, et al. Male sexual dysfunction. European Association of Urology Website. Accessed Jan 28, 2021. 

https://uroweb.org/guideline/male-sexual-dysfunction/

28. Higgins A, Nash M, Lynch AM. Antidepressant-associated sexual dysfunction: impact, effects, and treatment. 

29. Rothschild AJ. Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a drug holiday. 

30. Zajecka J. Strategies for the treatment of antidepressant-related sexual dysfunction. 

The sexual side effects of psychiatric medications are troubling enough that some patients consider treatment cessation. The authors review 5 strategies for managing sexual dysfunction.

Sex, Drugs, and Psychosis: Reviewing Psychiatric Medications’ Taboo Side Effect

Attention-deficit/hyperactivity disorder (ADHD) is frequently 

 other psychiatric conditions, including psychotic disorders. There is 

 for shared genetic susceptibility to both conditions,

 and first-degree relatives of people with ADHD have twice the risk of having schizophrenia compared with healthy controls.

There is also an added risk of psychosis in patients with comorbid cannabis use. There are overlapping environmental 

 for both disorders, including obstetric complications, preterm birth, and low birth weight.

 There are also abnormalities in overlapping dopaminergic brain circuits in schizophrenia and ADHD.4 However, epidemiologic evidence for the association between psychotic disorders and ADHD remains inconsistent.

 performed a systematic review and meta-analysis of the association between ADHD during childhood and the subsequent risk of developing a psychotic disorder. The authors searched MEDLINE, Scopus, PsycInfo, and Web of Science from inception through November 2015. They included peer-reviewed case-control and cohort studies of children younger than 18 with ADHD (using any recognized diagnostic criteria) with a comparison group.

The primary outcome was occurrence of any psychotic disorder (also using any recognized diagnostic criteria; including schizophrenia, schizophreniform disorder, brief psychotic disorder, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, or schizotypal personality disorder) at or after aged 18 years following a diagnosis of ADHD. They excluded studies with attention deficits or impulsivity without any ADHD diagnosis or adult ADHD diagnosis, or psychotic disorders that were diagnosed before or concurrently with ADHD. 

Relevant data—including relative risks (RR), odds ratios (OR), hazard ratios (HR), and 95% confidence intervals—were extracted for each study. An assessment of risk of bias and study quality was performed for each included study. Pooled measures of relative effects (eg, RR, OR, HR) were calculated using random-effects meta-analysis. Egger’s test and funnel plots were used to assess for potential publication bias. Subgroup and meta-regression analyses were performed for study design, sex, treatment, relevant psychiatric comorbidities, and type of outcome, but data were not available regarding substance use comorbidity.

The authors screened 3782 records and assessed 45 full-text articles for eligibility. After review, 15 studies (1 case-control and 14 cohorts) were included in the systematic review and 12 studies (1.85 million unique participants) were included in the meta-analysis. The median prevalence of 

 in the cohort studies was 0.5% for controls and 2.7% for the ADHD population, corresponding to an approximately 5-fold increased risk of subsequent psychotic disorder in children with ADHD (relative effect = 4.74, 95% CI 4.11-5.46).

Findings were similar in subgroup analyses (including schizophrenia versus other psychotic disorders, as well as the presence or absence of follow-up after aged 18 years). In meta-regression analyses, sex, and study quality did not moderate the association. There was no evidence of publication bias.

The authors performed the first meta-analysis of observational studies on the association between ADHD and psychotic disorders. They note that substance use disorder comorbidity is common to both conditions, and that the effects of 

 are also an important consideration, as there is inconsistent evidence on the possible association between chronic psychostimulant treatment and subsequent risk of psychotic disorder. 

There was inadequate data to consider effects of either substance use or psychostimulants in the present meta-analysis, and thus this information is relevant to future studies. They also note that psychotic symptoms and ADHD symptoms may overlap and can be confused and misdiagnosed (

). Strengths of the study included the large sample size and absence of publication bias. Limitations include clinical heterogeneity in the study populations, diagnostic criteria, and outcomes.

“Mr D” is a 21-year-old African American male outpatient at the community mental health center. He has a diagnosis of ADHD, combined type, and as a child, he received remote treatment with an unknown stimulant medication. His sister has depression, but his family history is otherwise unremarkable. At age 19, he was admitted for 1 week to the state psychiatric hospital because he had command auditory hallucinations for self-harm and began banging his head against the wall. He subsequently received a diagnosis of schizophrenia and cannabis use disorder. For the past year, he has been clinically stable on antipsychotic medication without additional psychiatric hospitalizations.

A childhood diagnosis of ADHD increased the risk of subsequent psychotic disorder almost 5-fold, independent of sex and diagnostic outcome (schizophrenia versus other psychotic disorder). Early detection (and management) of psychotic disorders in children with an ADHD diagnosis is essential.

1. Hamshere ML, Stergiakouli E, Langley K, et al. 

Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia

Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder

3. Linnet KM, Dalsgaard S, Obel C, et al. 

Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence

4. Howes OD, Kambeitz J, Kim E, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. 

5. Nourredine M, Gering A, Fourneret P, et al. 

Association of attention-deficit/hyperactivity disorder in childhood and adolescence with the risk of subsequent psychotic disorder: a systematic review and meta-analysis

There is evidence for overlapping risk factors and symptomatology between ADHD and psychotic disorders. New research investigates the association between ADHD during childhood and the subsequent risk of developing a psychotic disorder.









Examining the Relationship Between ADHD and Psychotic Disorders

Of the many canards directed against psychiatry in the late 20th century, one of the most enduring was the claim that psychiatric disorders are never included in pathology textbooks. For example, in 1998, a psychology professor confidently wrote: “If ‘mental illness’ is really a brain disease, it would be listed as such in standard textbooks on pathology. It is not listed as a brain disease because it does not meet the nosological criteria for 

However, as I argued in an article published more than 

 psychiatrists need not assert that the serious conditions we treat are brain diseases—only that conditions like schizophrenia and bipolar disorder represent bona fide disease, and that the term 

 is most usefully understood as a collection of highly distressing and dysfunctional conditions of individuals, not just their brains.

Brains, of course, may show cellular pathology, but this is merely the physical substratum of some 

 Cellular pathology is not disease in the holistic and experiential sense that so deeply concerns physicians and their patients. Indeed, those who argue that disease necessarily requires known structural abnormalities or cellular pathology should ponder this sweeping statement in the 8th edition of 

Harrison’s Principles of Internal Medicine

: “The clinical method has as its object the collection of accurate data concerning all the diseases to which human beings are subject; namely, all conditions that limit life in its powers, enjoyment, and duration.”

The editors go on to aver that the physician’s “primary and traditional objectives are utilitarian—the prevention and cure of disease and the relief of suffering, whether of body or of mind.”

In so arguing, the editors were implicitly invoking the 12th century physician-philosopher 

, who taught that “a physician does not treat a disease; he rather treats a sick person.”

Why Should We Care What Pathology Textbooks Say?

In my 2008 article, I presented several examples of pathology or neuropathology textbooks that recognized schizophrenia as a bona fide form of disease.

 In this article, I can update the list of pathology texts that clearly recognize schizophrenia as an instantiation of disease. To be clear: this is quite different than claiming that schizophrenia is a single, discrete disease like, say, pneumococcal pneumonia; it almost certainly is not.

Schizophrenia has been recognized as a form of disease for a long time. Eugen Bleuler, MD, referred to “the schizophrenias” (plural) more than 100 years ago, and most academics today see schizophrenia as a heterogeneous group of 

 as a kind of proxy for severe mental illness, which may include bipolar disorder, posttraumatic stress disorder, autism, and several other conditions.

But why bother with this exercise in the first place? I believe that the issue has great relevance to the place psychiatry occupies in the overall field of medicine. The voices of antipsychiatry are intent on extruding and excluding psychiatry from the realm of legitimate medical specialties, and they attempt to do so by denying that the conditions we treat qualify as genuine 

 Antipsychiatry invokes the putative authority of pathology texts to make its case, as if only pathologists can fathom the true nature of disease. This deification of pathology should be viewed as the triumph of scientism over science.

Pathology Texts that Recognize Schizophrenia

If some pathology textbooks recognize psychiatric conditions like schizophrenia as legitimate examples of disease, antipsychiatry’s case is radically weakened. With that in mind, here are some updated entries from several pathology texts that recognize schizophrenia as bona fide disease.

: “Multifactorial inheritance does not have a well-defined recurrence risks, but tends to run in families, and is more characteristic for diseases such as diabetes or schizophrenia.”

Practical Surgical Neuropathology: A Diagnostic Approach

: “Human disease is increasingly appreciated to have an underlying genetic basis. This is particularly true of neurologic disease, where genetic variants have been shown to increase risk or directly cause schizophrenia, autism spectrum disorder and neurodegenerative diseases.”

Pathology: Oxidative Stress and Dietary Antioxidants

: “Schizophrenia is a mental illness that comprises positive, negative and cognitive symptoms. Hyperactive dopaminergic signal transduction in the mesolimbic system and OS [oxidative stress] among other factors, are associated with the neurobiology of schizophrenia.”

: “There are no specific biochemical or morphological changes in common acquired mental diseases due to mental stress, strain, anxiety, overwork and frustration; eg, depression, schizophrenia.”

Note how this last sentence gives the lie to 3 cardinal (and bogus) tenets of antipsychiatry: 1) real disease must be physical or bodily, not mental; 2) real diseases must demonstrate specific biochemical or morphological deviations from normal; and 3) schizophrenia and depression are not real diseases. That the author views mental diseases as acquired due to mental stress is certainly open to revision and refinement, but this is no obstacle to considering schizophrenia a type of disease.

To be clear: the reality of psychiatric disease is not dependent on what textbooks do or do not include as diseases. That reality is demonstrated every day in the suffering and incapacity of 

 Nevertheless, it is important for psychiatry, as a profession, to correct the misrepresentations of its ill-informed critics—particularly those who seek to marginalize psychiatry by denying the reality of the diseases that grievously afflict our patients.

 is professor emeritus of psychiatry and lecturer on bioethics and humanities, SUNY Upstate Medical University; clinical professor of psychiatry, Tufts University School of Medicine; and Editor in Chief emeritus of 

. August 22, 1998:A12. Accessed April 22, 2021. 

2. Pies R. Psychiatric diagnosis and the pathologist's view of schizophrenia. 

3. Reese DM. Fundamentals--Rudolf Virchow and modern medicine. 

, 8th ed. G.W. Thorn et al, eds. McGraw-Hill; 1977.

5. Kottek SS. Toward becoming an accomplished physician: Maimonides versus Galen. 

7. Alnæs D, Kaufmann T, van der Meer D, et al. Brain heterogeneity in schizophrenia and its association with polygenic risk. 

Ronald W Pies, MD, considers the evidence from pathology textbooks—and answers the critics. 

Schizophrenia/Psychosis

Posters Indicate Potential Benefit for Patients With Schizophrenia

Late-Stage Pipeline Candidate Looks Promising for the Treatment of Schizophrenia

Sex, Drugs, and Psychosis: Reviewing Psychiatric Medications’ Taboo Side Effect

Examining the Relationship Between ADHD and Psychotic Disorders

Do Psychiatrists Treat Diseases?

Reconsidering Care and Coercion in Psychiatry: Kathleen Flaherty, JD

Extended-Release Risperidone Capsule Making Waves

Phenomenology, Power, Polarization, and Psychosis

Psychiatric Treatment: Side Effects Basics

Dementia-Related Psychosis Treatment Receives Complete Response Letter