Hero

Videos

Slideshows

Articles

Podcasts

Poll

There is increased recognition of sex differences in the epidemiology and phenomenology of 

. For example, compared with males, females have a slightly lower incidence of the disorder, a later age of onset, and more depressive symptoms.

 Such sex differences may be mediated, in part, by the neuroprotective effects of estrogen.

 By contrast, findings regarding sex differences in cognition in schizophrenia are inconsistent.

 Insomnia is also common in the clinical course of schizophrenia.

 In the general population, insomnia is associated with greater cognitive impairment, but its association (and potential sexual dimorphic effect) in schizophrenia is less clear.

“Ms Smith” is a white woman, aged 50 years, with a 20+ year history of schizoaffective disorder, bipolar type, and a remote history of a cerebellar hemorrhagic stroke. She has been on a stable dose of antipsychotic medication for the past 10 years, prior to which a clozapine trial was discontinued due to tolerability and adverse effects. She chronically sleeps 3 to 5 hours per night, with both initial and terminal insomnia. She has chronic auditory hallucinations, thought insertion, and persecutory beliefs. She also has chronic cognitive impairment, thought to be in part due not only to her chronic psychotic illness, but to a sequela of the past cerebellar infarct. She graduated with a 2-year technical degree after high school. She has completed different forms of the Digit Symbol Coding test at multiple outpatient psychiatric clinic visits over the years, with a mean (SD) score of 31±4. A trial of adjunctive electroconvulsive therapy for residual positive symptoms of psychosis was discontinued due to exacerbation of cognitive impairment.

Zhu and colleagues investigated sex differences in insomnia and cognition in a large sample of Chinese patients with chronic schizophrenia.

 They recruited 718 patients (480 males and 238 females) with chronic schizophrenia from 2 psychiatric hospitals, along with 397 healthy controls (169 males and 228 females) without a personal or family history of psychiatric or neurological disease. Inclusion criteria for patients were age 17 to 70 years; Chinese Han ethnicity; DSM-IV diagnosis of schizophrenia; and stable antipsychotic dose for > 6 months. Patients were excluded if they had any of the following: a history of neurological disease or drug or alcohol abuse; current severe medical comorbidity; head injury; or current pregnancy or lactation.

Insomnia was assessed as both a categorical (yes/no) and a continuous measure with the Insomnia Severity Index (ISI). Symptoms were rated using the Positive and Negative Syndrome Scale (PANSS). Cognition was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The authors used 2 x 2 ANOVA (insomnia x sex) and Spearman correlation coefficients to investigate sex differences in clinical variables in patients with and without insomnia.

The mean subject age was 46 years. There was a significantly increased prevalence of (categorical) insomnia in females vs males with schizophrenia (25.6% vs 18.3%; OR, 1.54). Females with schizophrenia also had significantly higher PANSS total and subscale scores. Males with schizophrenia had higher (better) RBANS total, visuospatial/constructional, and language scores than females. In both males and females with schizophrenia, patients with (categorical) insomnia had higher PANSS scores than those without insomnia. By contrast, there was no difference in RBANS scores in males with vs without insomnia. However, females with insomnia had lower RBANS total and subscale scores. As a continuous measure, ISI scores were significantly, negatively correlated with RBANS total scores, language, attention, and delayed memory scores in males (P = –.14 to –.12 for each). By contrast, ISI scores were significantly negatively correlated with RBANS total scores (P = –.18) and immediate memory (P = –.19) scores in females.

The authors concluded that females with schizophrenia had an increased prevalence of insomnia and greater cognitive impairment than males. They also found sex differences in correlations between insomnia and cognition in these patients. Study strengths included the large cumulative sample size. Study limitations included the cross-sectional study design and the nonstandardized antipsychotic (and other) medications in the study sample. Future studies should consider associations between insomnia and cognition using a longitudinal design and also in first-episode and antipsychotic-free patients with schizophrenia.

Findings support evidence for sex differences in insomnia and cognition in patients with schizophrenia. Given its association with more severe symptoms and greater cognitive impairment, insomnia represents an important potential treatment target in this patient population.

is a professor in the Department of Psychiatry and Health Behavior of Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

Sex and gender differences in schizophrenic psychoses

Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review

Oestrogens, prolactin, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses

Prevalence of insomnia and clinical and quality of life correlates in Chinese patients with schizophrenia treated in primary care

Sex difference in association between insomnia and cognitive impairment in patients with chronic schizophrenia

“In the general population, insomnia is associated with greater cognitive impairment, but its association (and potential sexual dimorphic effect) in schizophrenia is less clear.”

Insomnia and Cognition in Males vs Females With Schizophrenia

The Split Mind: Schizophrenia from an Insider’s Point of View

, author Kevin Alan Lee asserts that the health care system fails when doctors are unable to treat an illness that is treatable. In psychiatry, this failure was an all-too-common occurrence for decades. We are fortunate that there are now more treatment options than ever before for serious mental illnesses, and that many diseases once deemed untreatable can now be managed.

Schizophrenia is a good example of a condition for which there are many available treatments. Different individuals respond better to different treatments, and a treatment that is right for an individual today might not be the best fit for them in a year or a decade. The challenge—or opportunity—we face today involves working with individuals who are living with mental illness and their loved ones to find the right treatment at every step along their disease and life journey.

Understanding Schizophrenia and Treatment

A complex and difficult-to-treat brain disorder, schizophrenia affects about 1% of the US population.

 Typically, symptom onset occurs in young adulthood and can include hallucinations, delusions, disorganized thinking, and behavior associated with psychosis. If left untreated, schizophrenia can have a distressing impact on a person, as well as their family and friends.

Most people living with schizophrenia require long-term pharmacological treatment, along with psychosocial therapy, to help manage their disease. Since schizophrenia is a chronic condition, long-term disease management should be tailored to the needs and preferences of the patient to best ensure consistent symptom control.

 Disease relapse is a significant challenge in the treatment of schizophrenia, so, as a physician, one of my top concerns is if my patients will continue to take their medication as prescribed.

 This is why I discuss with each patient their overall treatment goals and then the pros and cons of different antipsychotic treatment options available to them. I include in this discussion the 2 main categories of medication delivery: oral and long-acting injectable, which are briefly outlined below.

Oral antipsychotic drugs (OAPs) are widely prescribed to treat many psychiatric conditions in addition to schizophrenia, including bipolar disorder and autism, and as augmentation for major depressive disorder.

OAPs offer people easy-to-use daily medications to reduce symptoms of mental illness.

 However, these medications may cause side effects, including neurological events such as involuntary muscle contractions or, more rarely, tardive dyskinesia. In many cases, these side effects can be managed successfully and will go away after a short period of time.

Atypical OAPs are newer treatment options developed with the goal of delivering effective symptom control with fewer side effects.

 Even so, these medications have come under some scrutiny because they may cause side effects, including weight gain and metabolic adverse effects.

OAPs are the best choice for many individuals. For instance, I had a patient with exacerbated psychosis and schizophrenia. After discussing available treatments, his fear of needles, and his previous medical history, he decided an OAP was right for him. We found a medication that worked well to control his symptoms with less severe side effects than other treatments he previously tried. He is now a part-time employee, living and volunteering in a group home as a peer advocate who engages others about how manageable conditions like schizophrenia can be.

Different treatments address diverse clinical and lifestyle needs for those living with schizophrenia. Research findings have shown nonadherence rates of up to 68.8% among individuals receiving OAPs for the management of schizophrenia.

 Long-acting injectables (LAIs) were designed to support continuity of treatment.

Formulated to maintain stable therapeutic blood levels during the period between injections (most often every 4 to 8 weeks), LAIs reduce the need to for individuals to remember to—or be reminded to—take their medication and can enhance autonomy.

 LAIs can also reduce the risk of unintentional or deliberate overdoses by offering clinicians transparency if patients fail to take their medication.

Studies have shown that LAIs may lower risk of hospitalization or relapse compared to OAPs.

 However, LAIs do come with considerations, including less flexibility in dosing adjustment and side effects, including pain at the injection site, or leakage of the drug into the subcutaneous tissue that causes irritation and lesions.

LAIs are an important treatment option for some individuals. One patient of mine, a 20-year-old straight-A college student, came to us for a manic episode presenting with psychosis. While in the hospital, she received an injection that gave her relief from the distress, paranoia, agitation, and fear that she was feeling. The autonomy that an LAI offered represented the right ongoing treatment choice for her. She has graduated college, become an advocate for others with serious mental illness, and is founding a startup company.

It is important to note that, in the past, LAIs were sometimes used in inpatient settings to ensure medication compliance. This has led some people to view injections as punitive. Some clinicians believe that patients will react negatively to the idea of an injection, which may lead them to avoid discussing this option. However, to prescribe medications that best align with patients’ goals, we must overcome this and work together with our patients to explore all possible treatment options—both their benefits and their drawbacks.

Because of innovations in psychiatry, there are now fewer “untreatable” diseases. Symptom control is critical to well-being in mental illness, but we cannot forget patients’ goals or needs. It is important for physicians and patients to establish genuine rapport, carefully weigh treatment options, and develop a plan that ensures the patient has the right treatment at the right time in their journey.

is chief medical officer of Athena Care located in the Nashville area, where he often works with patients with schizophrenia.

Schizophrenia: opportunities to improve outcomes and reduce economic burden through managed care

2. Miyamoto S, Wolfgang Fleischhacker W. 

The use of long-acting injectable antipsychotics in schizophrenia

3. Biagi E, Capuzzi E, Colmegna F, et al. 

Long-acting injectable antipsychotics in schizophrenia: literature review and practical perspective, with a focus on aripiprazole once-monthly

Newer oral atypical antipsychotic agents: a review

5. Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. 

Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

 [published correction appears in Lancet. 2019 Sep 14;394(10202):918]. 

. Updated June 29, 2018. Accessed March 3, 2022. 

https://patient.info/mental-health/schizophrenia-leaflet/antipsychotic-medicines

A narrative meta-synthesis of how people with schizophrenia experience facilitators and barriers in using antipsychotic medication: Implications for healthcare professionals

Antipsychotic long-acting injections: mind the gap

9. Brissos S, Veguilla MR, Taylor D, Balanzá-Martinez V. 

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

10. Kishimoto T, Hagi K, Kurokawa S, et al. 

Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies

How do we find the right treatments for our patients with schizophrenia at every step of their journey?

Schizophrenia: Current Treatment Options and Considerations

A recent study determined hyperprolactinemia (HPRL) was not associated with taking antipsychotic drugs with high expected HPRL risk.

HPRL is a side effect of some antidepressants and antipsychotics. HPRL is frequently observed in patients with schizophrenia and can also occur in Hashimoto's thyroiditis due to the prolactoliberin effect of thyroliberin. In women, it may present with decreased libido, infertility, oligomenorrhea/amenorrhea, and galactorrhea; in men, it may present with decreased libido, infertility, gynecomastia, or impotence.

In the recent study, patients with comorbid schizophrenia and Hashimoto's thyroiditis who received antipsychotics were of special interest, as these patients have higher risks of HPRL. Investigators sought to analyze risks of HPRL with antipsychotic treatment, identify an association between the antipsychotic therapy and HPRL in Hashimoto's patients receiving antipsychotic therapy, and explore the association of HPRL in patients with Hashimoto's thyroiditis and schizophrenia during antipsychotic therapy.

Investigators examined 17 participants with comorbid schizophrenia receiving antipsychotic therapy, all euthyroid or with light hypothyroidism. They analyzed different laboratory parameters, including anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies, blood levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and prolactin (PRL).

Results revealed high levels of PRL, and anti-TPO and anti-TG autoantibodies. Patients were then classified into 3 groups by the degree of expected HPRL risk from antipsychotics: without risk, with low risk, and with high risk. The correlation analysis detected an inverse significant correlation (R=-0.51; p=0.037) between expected level of drug-associated HPRL risk and actual PRL levels in the group. At the same time, we detected a positive significant correlation between the levels of PRL and FT4 in the groups (R=0.53; p=0.03). Correlations between PRL levels and other parameters such as TSH, FT3, anti-TPO, anti-TG, anti-TSH receptor antibodies were not statistically significant.

HPRL in the group was not associated with taking of antipsychotic drugs with high expected HPRL risk. Yet, a significant positive correlation existed between the levels of PRL and FT4. Hence, in Hashimoto's thyroiditis accompanied with treated mental illness there are some non-iatrogenic stimulants of prolactogenesis.

“It cannot be ruled out that antipsychotics may interfere with prolactin metabolism, which creates a false effect of a positive correlation between prolactin and free thyroxine levels, in contrast to common HPRL of hypothyroidism,” concluded the authors.

1. Sobolevskaia PA, Churilov LP, Fedotkina TV, et al. 

Hyperprolactinemia and antipsychotic therapy in schizophrenic patients with Hashimoto's thyroiditis.

Clinical presentation of hyperprolactinemia.

A recent study examined hyperprolactinemia and antipsychotic therapy in patients with schizophrenia and Hashimoto's thyroiditis. 

Hyperprolactinemia and Antipsychotic Therapy in Patients With Schizophrenia

A study identified an urgent need for more research in the assessment, reporting, and treatment of pain in individuals with severe mental illness (SMI).

The study, an evidence review accepted for publication by the International Association for the Study of Pain (IASP), focused on the diagnostic challenges of pain management in individuals with bipolar disorder, psychosis, and major depression, and suggested potential treatment methods to improve pain management in these individuals.

 The investigators noted that pain commonly cooccurs with depression, but pain prevalence estimates in individuals with depression vary significantly (15% to 100%; mean 65%). The investigators also noted that there is a high prevalence of pain in individuals with bipolar disorder. They cited 1 meta-analysis (

=22) stating that 29% of participants with bipolar disorder (

=171,352) reported experiencing pain—which was more than double the pain risk noted for the healthy controls (

=12,342,577). They mentioned that many studies in the review relied on unvalidated assessments of pain, which may have affected the results.

The investigators also noted a complex relationship between pain and psychosis, with varying reports of pain in individuals with schizophrenia. Some meta-analyses report that these individuals have higher pain thresholds, although 1 study (

=14) found that 35% of participants with schizophrenia (

=242,703) reported experiencing clinical pain at levels similar to the sex- and age-matched controls without mental illness (

=4,259,221). The investigators also noted that associated risk factors, such as diabetes and obesity, may lead to these individuals underreporting or underrecognizing pain, even though another study of individuals with psychosis (

=438) found an association between clinically relevant pain and comorbid depressive symptoms. The investigators concluded overall that reports of pain may be diagnostically specific, psychosis may be associated with underreporting pain, and comorbid depression may be associated with more reports of pain.

As the understanding of pain—especially its biopsychosocial influences—in these patient populations and associated research is limited, the investigators suggested several psychological treatments for pain in individuals with SMI; these treatments have been increasingly supported by research. Specifically, the investigators noted cognitive-behavioral therapy (CBT), family and caregiver interventions, and exercise-based treatments—given that both SMI and persistent pain are associated with low physical activity—may be effective treatments to help mitigate pain in individuals with SMI. The investigators also concluded that there is an urgent need for more research in this area, and that improvements need to be made in the recognition and assessment of pain in these individuals; stakeholder involvement (ie, caregivers, mental health professionals); implementation science; and individualized evaluation and treatment.

“There is an urgent need to advance research and practice to improve pain management in people with SMI,” the investigators concluded. “This work should draw on synergies in the existing evidence for managing pain and SMI. Meaningful involvement of people with lived experience is essential to advance this agenda.”

Urgent need for more research and focus on treating pain in people with severe mental illness, new evidence review shows

. News release. Wolters Kluwer. March 22, 2022. Accessed April 13, 2022.

2. Onwumere J, Stubbs B, Stirling M, et al. Pain management in people with severe mental illness: an agenda for progress. 

. Published online ahead of print March 16, 2022. Accessed April 13, 2022.

Evidence review focuses on bipolar disorder, psychosis, and major depression.

Study Identifies Urgent Need for More Research on Pain in Severe Mental Illness

John H. Krystal, MD, discusses the new FDA approval of BioXcel Therapeutics' dexmedetomidine (Igalmi™) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. To read more abou this approval, see "

New Approval for Treatment of Agitation Associated with Schizophrenia or Bipolar I or II Disorder.

is the Robert L. McNeil, Jr. professor of translational research; professor of psychiatry, neuroscience, and of psychology; and codirector at the Yale Center for Clinical Investigation. He also serves as chair and chief of psychiatry at Yale-New Haven Hospital. He is also the director of the NIAAA Center for the Translational Neuroscience of Alcoholism, and director of the clinical neuroscience division at the VA National Center for PTSD.

How is this new drug going to help in the treatment of agitation in patients with schizophrenia or bipolar disorder? 

Treating Agitation: A New FDA Approval 

TALES FROM THE CLINIC: THE ART OF PSYCHIATRY

Tales From the Clinic: The Art of Psychiatry

, we delve into the world of psychosis and the accompanying suffering from a psychodynamic and suicide risk perspective. Chronic psychotic disorders, exemplified by schizophrenia, bring about terrible suffering and are not fully treatable. Despite advances in psychiatry, we have limited treatment options to offer that can lead to true recovery. Shattered lives ensue, with all the sadness attached. The clinicians who treat this challenging population deserve all our gratitude and support.

“Mr Thomas” was a young male in his late 20s when he first presented at our community clinic to establish care. He was accompanied by his father during the first visit and in all subsequent follow-up appointments. Mr Thomas was visibly shy and anxious during the first appointment. He sat quite close to his father, mostly avoided any eye contact with his psychiatrist, and often deferred to his father for most of the answers. He later revealed the reason for the lack of eye contact was his effort to block the intrusive “inappropriate sexual thoughts” when seeing someone; looking at the psychiatrist would make him think and imagine his naked body. Despite the palpable shyness and anxiety present in the first visit, Mr Thomas gave the impression that he was familiar with outpatient psychiatric care since he had been seeing psychiatrists for years, first for anxiety when he turned 20, and later for bizarre thoughts.

Soon after the fall semester of his junior year, he started having delusional thoughts that he was responsible for the firing of a few employees at a local newspaper because of his hacking into their website and him providing rude feedback on their job performance. In addition, Mr Thomas’ self-esteem and sense of belonging took a major hit because he frequently believed he was causing trouble to others. During one visit, Mr Thomas said he had not slept well the night before because he believed that his neighbor’s dog was barking at him all night to tell him how bad he was and that he would get into trouble. Mr Thomas also talked about his ruminating fear that he would become a pedophile one day due to his intrusive sexual thoughts about children—and, even worse, that his “bad” thoughts could infect others.

The psychotic episodes quickly turned into a distressing experience and sank him further into disorganized thoughts and behaviors. Late in the spring semester of his junior year, Mr Thomas was hospitalized for disorganized behaviors, poor self-care, and suicidal thoughts. Subsequent psychotic episodes and hospitalizations rendered him a harsh reality of a long and seemingly unending struggle with severe schizophrenia.

Nonetheless, despite going through a few more psychotic episodes in the following years, he was able to complete his college degree. In contrast to the sullen look he had when talking about the mental health illness that derailed his life, Mr Thomas spent time during a few visits recalling his childhood and his early years of college with a lot of fondness. Also, behind the flat affect, the self-doubt, and the suffering, Mr Thomas was a deeply caring individual; he regularly donated a significant part of his monthly Social Security check to a local food bank. In one visit, he expressed extreme relief after learning his intrusive thoughts were not contagious and that he was not responsible for others having obsessive compulsive disorder because of his presence. However, when it came to his emotional suffering and daily life struggle, Mr Thomas rarely spontaneously spoke or elaborated when asked.

It has been 5 years since Mr Thomas moved back home after college to live with his father, who has always been a loving and caring figure, but life was not any easier for Mr Thomas. Initially, he was able to find a few labor jobs, but he struggled to hold them: “I do not want to be working around people.” Mr Thomas said he used to be a social person in college, but now he no longer had any meaningful relationships outside of his immediate family. He had not been in touch with his old friends in recent years. The interplay of cognitive, behavioral, and emotional dysfunctions of schizophrenia has led to a long-term impairment of his social and occupational functioning, sinking Mr Thomas into further loneliness, isolation, and a lack of a sense of belonging.

Mr Thomas had been on multiple atypical antipsychotic trials in his earlier years of treatment for psychosis, but the treatment did not make a meaningful impact on his positive symptoms. At the time of his first visit to our clinic, he was already on clozapine; this medication seemed to help with his delusional thoughts of him causing harm to others. However, he still occasionally developed the fear of ruining others’ minds because he believed that they could hear his “bad” thoughts. Also, the intrusive thoughts and images of seeing others in sexual ways continued to torment him, causing a lot of shame and guilt.

Besides taking sertraline for depression, he also had weekly psychotherapy, mostly focusing on cognitive behavioral therapy for psychosis and intrusive thoughts. He found the intervention beneficial, at least partially. At one point, Mr Thomas was able to go to the park and challenge his fear of making eye contact with people by greeting them; however, the intrusive thoughts and imagining others naked never seemed to go away.

Prior to taking sertraline, he was also on fluvoxamine, but it did not have any impact on the intrusive thoughts, even at the highest dose. When the intrusive thoughts became unbearable, Mr Thomas said he sometimes chose to sleep most of the day, so he did not have any awareness of his thoughts and feelings. Mr Thomas’ fears could be more consistent with anxieties higher on the developmental hierarchy. Even though the experience of emerging psychosis during his college years seemed to be devastating, as it burdened the ego with primitive anxieties and deteriorating, his suffering from the psychosis seemed to be much worse in its later stage due to the loss of old self and the confusion of a new one.

Throughout the clinic visits, a sense of loss and grief over the old self was palpable. At one point, Mr Thomas mentioned with a profound sadness that he used to have many hobbies as a teenager. In one visit, he also proudly talked about being selected for his college swim team. These days, he still occasionally went out and swam at a local YMCA, but only when the intrusive thoughts were not troubling him. Otherwise, he spent his time at home checking emails or going to a local library when he did not feel like he was causing problems to others.

Anxiety, guilt, and shame could be unbearable for Mr Thomas at times because of the ruminating thoughts. To him, the thoughts were totally inappropriate; they seemed as if they were part of him, not his illness, especially when he talked about seeing the flash of someone’s genitalia when making eye contact with them. To cope with it, he avoided leaving his house altogether. The only time of the day when he found peace was late at night, walking his family’s dog when there was no one around him.

He never considered using substances to cope with the mental suffering. Mr Thomas belonged to the minority of patients with schizophrenia who never used, misused, or abused any substance, including tobacco, to self-soothe. Research has shown that a history of substance use disorder is associated with a 1.5- to 2-fold increase in suicide rates among patients and can lead to a decrease in executive functioning abilities and a subsequent increase in impulsivity during the course of the disease.

Over the years, the missing sense of belonging and the confusion between his thoughts and reality made him feel increasingly hopeless and helpless. How could he find the future worth looking forward to when he lost his old self? As his psychotic process progressed, more primitive anxieties developed, such as disintegration anxiety and annihilation anxiety. Mr Thomas began to experience the self as formless and diffuse, and thoughts and perceptions became difficult to differentiate.

The container by which patients suffering from severe schizophrenia relate to the outer world has lost its structure. For Mr Thomas, the experience was now not so much of annihilation anxiety, but about himself slipping away and disintegrating. The terror itself can become a companion, providing reassurance that something of the self remains.

Mr Thomas frequently felt indifferent about death because he thought his existence was a burden to himself and everyone else. Mr Thomas drifted further into hopelessness, helplessness, and isolation, despite the love and care from his family, because of the loss of control, the confusion, and the lack of a sense of belonging.

Now, as a young man in his late 20s, Mr Thomas continued the long struggle in his day-to-day existence. The highest risk of completed suicide is recorded among individuals with onset of illness between the ages of 22 and 24 years.

Coupled with the guilt and shame that was exacerbated by his delusional thoughts, the anguish and torment from his suffering became unbearable on multiple occasions. Mr Thomas had been hospitalized 5 times in the 5 years since establishing care at our clinic. Three of these hospitalizations were for having suicidal thoughts, and the other 2 were for serious suicide attempts: one by overdosing on his psychiatric medication, and the other by drowning himself in a swimming pool.

Patients experiencing psychotic symptoms are more likely to exhibit feelings of shame, stigma, guilt, and rejection. Independently, these feelings lead to exacerbation of one’s symptoms, increased social withdrawing, reluctance to seek help, and subsequently a greater risk of completed suicide attempts. Previous suicide attempts are generally considered the number-1 risk factor for subsequent death from suicide. Among patients with schizophrenia, a history of previous attempts early in the treatment period or in the pretreatment period necessitates immediate intervention.

Mr Thomas’ suffering from shame and guilt never seemed to end because of ongoing intrusive sexual thoughts. During one psychotic episode, Mr Thomas felt horrible about himself for having a sexual thought that was transmitted to his right-side neighbor through the vents in his bathroom. The psychotherapy intervention on his delusions and intrusive thoughts was not as effective due to Mr Thomas’ concrete thought process and increasingly poor insight. The effect of insight alone can be paradoxical, as it contributes to the illness’ severity through the mediating effects of depression and hopelessness.

 Living with a diagnosis can make it hard for him to separate his identity from it, leading to feelings of hopelessness, loss of autonomy, negative views of oneself, and demoralization. These factors, combined with maladaptive coping mechanisms and lack of social support, can lead to depressive feelings and internalized stigma at a later stage of the disease.

Although a hospital stay can have positive effects on one’s illness, by ensuring adequate management, symptomatic control, and greater security, studies have shown a higher rate of completed suicide in the week following discharge. Patients lacking adequate support outside of a health care facility could be faced with more hardships upon discharge. Some could also view their illness as more debilitating when it requires a longer course of hospitalizations, leading to less adherence with the course of treatment.

A deeper understanding of patients’ suffering—especially through the view of the often-ignored psychodynamic lens—and early recognition of suicide risk factors specific to patients with schizophrenia are important in clinical settings. The effective intervention relies on detection and treatment tailored to each patient’s needs, rendering the healing journey more bearable and less challenging.

is an assistant professor in the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and director of Community Psychiatry Clinics at the Harris Health System in Houston, Texas. 

is a medical student at the University of Balamand, Lebanon, who plans to pursue a residency in psychiatry. 

 is a clinical assistant professor at Baylor College of Medicine and a child, adolescent, and adult psychiatrist in private practice in Houston, Texas.

Psychodynamic Psychiatry in Clinical Practice. 5th ed

2. Lähteenvuo M, Batalla A, Luykx JJ, et al. 

Morbidity and mortality in schizophrenia with comorbid substance use disorders

3. Lingiardi V, McWilliams N, eds. Predominantly psychotic disorders. In: 

Psychodynamic Diagnostic Manual – 2nd edition: PDM-2

Predictors of suicide at time of diagnosis in schizophrenia spectrum disorder: a 20-year total population study in Ontario, Canada

Association of an early intervention service for psychosis with suicide rate among patients with first-episode schizophrenia-spectrum disorders

6. Acosta FJ, Navarro S, Cabrera B, Ramallo-Fariña Y, Martínez N. 

Painful insight vs. usable insight in schizophrenia. Do they have different influences on suicidal behavior?

How can looking at the suffering of patients with schizophrenia through a psychodynamic lens help clinicians develop effective interventions and treatment plans?

Shattered Self: Schizophrenia Suffering, Beyond Logic and Reason 

Today, the US Food and Drug Administration (FDA) approved BioXcel Therapeutics dexmedetomidine (Igalmi™) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

 Dexmedetomidine can be self-administrated by patients under the supervision of a health care provider.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for health care professionals to treat,” said John Krystal, MD, the Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry at Yale School of Medicine. “The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides health care teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option.”

Dexmedetomidine’s approval is based on data from 2 pivotal randomized, double-blinded, placebo-controlled, parallel group phase 3 trials: SERENITY I and SERENITY II. These trials evaluated dexmedetomidine for the acute treatment of agitation associated with schizophrenia (SERENITY I), and bipolar I or II disorder (SERENITY II).

The primary endpoint was mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score. Change was assessed 2 hours following dosing. The secondary endpoint was to find the earliest time where efficacy, measured by the change from baseline in PEC score, was statistically separated from placebo.

Dexmedetomidine met the primary endpoint in both trials at 2 hours after the first dose in patients treated with the 120 mcg and 180 mcg doses, demonstrating statistically significant improvements from baseline. IGALMI also met the key secondary endpoint, with statistically significant separation from placebo observed at 20 minutes for both the 180 mcg and 120 mcg doses in SERENITY II and 20 minutes and 30 minutes in SERENITY I.

“IGALMI is the first new acute treatment for schizophrenia or bipolar disorder-associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics.

BioXcel is prepared to launch dexmedetomidine in the US in the second quarter of 2022.

1. BioXcel Therapeutics announces FDA approval of IGALMI™ (dexmedetomidine) sublingual film for acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. BioXcel. News release. April 6, 2022. 

https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-fda-approval-igalmitm

The FDA has approved dexmedetomidine sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

New Approval for Treatment of Agitation Associated with Schizophrenia or Bipolar I or II Disorder

“Charlie” is an 18-year-old Caucasian male with recently diagnosed bipolar disorder. He has no significant family psychiatric history. His early growth and development was typical, although he was a colicky baby. In early elementary school, he was demanding and outspoken, with increased energy. At age 10, his parents noticed some mood changes and that he was overly sensitive. Charlie had worsening mood lability at age 13, with periods of irritability and depression. At times, he was active and bossy on the playground—other times, he preferred to isolate inside and read during recess. He had some intermittent sleep difficulties and periodic anger outbursts at home. He also occasionally reported some unusual experiences. At age 16, his symptoms dramatically worsened, and he was hospitalized for a first episode of mania.

There is a recent increased effort to identify at-risk subjects for major psychiatric disorders, including 

 and bipolar disorder, and to predict individuals with prodromal symptoms who will progress to full-threshold disorder.

 First-episode mania (FEM) has been less frequently studied than first-episode psychosis (FEP). Furthermore, studies of FEP do not typically distinguish between affective and non-affective FEP,

 Risk/vulnerability markers include a family history of mood disorders and 

 for bipolar disorder, perinatal complications, worse premorbid adjustment, and increased 

 aimed to identify symptomatic and temporal differences between the prodromal phases of FEM and FEP with onset in young adulthood or adulthood, as well as differences in risk factors and vulnerability markers. The authors performed a retrospective cross-sectional analysis, as part of a larger 2-year study in Spain. Diagnosis was confirmed using a semi-structured interview according to DSM-5 criteria. Inclusion criteria were outpatients aged 18 to 45 and a FEM or FEP in the past 4 years. They excluded subjects with intellectual disability, severe medical conditions (eg, HIV or cancer), alcohol or other substance dependence, or 

Data on clinical features at illness onset, current clinical symptoms and treatments, and medical histories were collected. Data on prodromal symptoms (within 3 years of onset) were obtained retrospectively from patients (and caregivers), including using the semistructured Bipolar Prodrome Symptom Scale-Retrospective. Data on risk factors, including family history of psychiatric disorders, life stressors, childhood trauma, delayed language or psychomotor development, nocturnal enuresis, and difficulties in writing and reading were assessed. Clinical information on mental health services during youth (including diagnoses and medications) were also obtained. Logistic regression models were used to investigate prodromal symptoms as predictors of FEM and FEP. Differences in the duration of prodromal symptoms in FEM and FEP were assessed using Student’s t-test.

The study sample included 108 subjects (n=72 with FEM and n=36 with FEP). There were no sociodemographic differences between subject groups, except worse psychosocial functioning in patients with FEP. Subjects with FEM had a significantly shorter duration of untreated psychosis. There were no significant differences in the number of total prodromal symptoms between FEM and FEP. Social isolation was significantly associated with the prodromal stage of FEP, and increased energy or goal-directed activity with the prodromal stage of FEM. FEP was associated with a longer and more gradual onset and slower deterioration than FEM. The depression symptom “physically slowed down” was most associated with a gradual onset pattern, whereas “increased energy” was most associated with more rapid onset. There were higher rates of obstetric complications and reading/writing difficulties in FEP than FEM. Impaired premorbid adjustment was characteristic of FEP; otherwise, there were no differences in vulnerability factors.

The authors concluded that different clinical symptoms were associated with the prodromal phases of FEP and FEM; FEP was associated with a longer prodrome; reading/writing difficulties differentiated FEP and FEM; and impaired premorbid adjustment was more characteristic of FEP. The main study strength was the use of comprehensive and exhaustive assessments. Study limitations included the relatively small sample size (particularly for FEP) and the potential for recall bias with retrospective assessments.

The psychosis and mania prodromes, coupled with risk and vulnerability markers, may contribute to identification of individuals at increased risk of conversion to fulminant disorders. Together, this information may help identify targeted early treatment strategies based on individual characteristics.

is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

1. Arango C, Díaz-Caneja CM, McGorry PD, et al. 

3. Barajas A, Pelaez T, González O, et al. 

Predictive capacity of prodromal symptoms in first-episode psychosis of recent onset.

4. Fusar-Poli P, Cappucciati M, Rutigliano G, et al. 

Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta-analysis.

5. Verdolini N, Borras R, Sparacino G, et al. 

Prodromal phase: differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood.

Predicting mania versus psychosis: Researchers performed a retrospective study of prodromal symptoms, risk factors, and vulnerability markers in first-episode mania and psychosis.

Prodromal Mania and Psychosis

A new cross-sectional observational study evaluated the risk perception of the COVID-19 pandemic in Italian patients with a mental health diagnosis to better understand how they faced the pandemic. Results showed that individuals with a mental illness may be more likely to engage in risky behavior.

Investigators conducted their research during the second wave of the COVID-19 pandemic and the lockdown in Italy, assessing risk perception and risk-related variables in a sample of 150 participants with a previous diagnosis of major depression, bipolar I disorder, and schizophrenia. Results showed that participants were more concerned about economic, psychological, and interpersonal consequences of COVID-19 than about physical health.

“Our study highlights the need to provide more support to psychiatric patients during emergency events to prevent them from engaging in risky behaviors,” wrote the authors.

Findings showed no difference in the perception of risk among patients with major depression, schizophrenia, and bipolar disorder. This may indicate that mental illness might influence risk perception independently from the diagnosis, as is indicated by previous studies that demonstrated mental illness influences patient’s well-being and daily living.

 Furthermore, patients with severe mental illness have higher risk of developing COVID-19, perhaps due to a lack of a sense of self-preservation.

Participants reported a higher perceived risk of work and of economic consequences due to COVID-19 pandemic. Data on mortality risk showed that patients considered the risk of dying for heart attack, cancer, and stroke higher than the risk of dying for COVID-19, perhaps due to participants’ high perception of control, self-efficacy, and positive emotions toward the COVID-19 pandemic. Participants were more concerned about the negative impact of the pandemic on psychological well-being and interpersonal relationships.

“Our results showed that psychiatric patients perceived the economic and social long-term consequences of COVID-19 much more dangerous than the short-term ones (contagion, death, and health risk). In addition, the increase in knowledge about the virus accentuates these concerns. We believe that it is necessary to develop new interventions to implement coping strategies aimed to reduce the impact of emergency situations on the psychiatric population,” said the authors.

1. Natale A, Concerto C, Rodolico A, et al. 

Risk perception among psychiatric patients during the COVID-19 pandemic.

2. Momen NC, Plana-Ripoll O, Agerbo E, et al. 

Association between mental disorders and subsequent medical conditions.

Patients with mental health disorders in the COVID-19 epidemic.

The risk and prevention of novel coronavirus pneumonia infections among inpatients in psychiatric hospitals.

Patients with bipolar I disorder and other mental illnesses may be at increased risk for COVID-19 infection. 

Too Risky? Mental Illness and Risky Behaviors During the COVID-19 Pandemic

“Mr Spear” is a 43-year-old Caucasian male with a 20-year history of schizophrenia who presents for an initial outpatient appointment. Mr Spear’s primary complaint is 

. Upon further questioning, he explains that he is afraid to sleep due to paranoia that there are people outside his home at night who want to kill him while he is asleep. He is adamant that he will not take any medication that makes him drowsy. His mental status is otherwise unremarkable. He denies any suicidal or homicidal ideations, and he does not appear to attend to internal stimuli. He reports several previous psychiatric hospitalizations, but none in the past 3 years. He works full-time in construction and denies any work-related problems. After a discussion of risks and benefits, he agrees to a trial of low-dose aripiprazole daily (morning) and to return to the clinic in 4 weeks. However, Mr Spear is a no-show for his follow-up appointment, he does not return a phone call to reschedule, and he never returns to the clinic.

Decreased adherence to antipsychotic treatment is common in schizophrenia and associated with poorer outcomes, including illness relapse, cognitive impairment, substance use, 

 Estimates of antipsychotic adherence in schizophrenia vary widely, and there is evidence that objective methods (eg, pharmacy refill records or blood levels) yield significantly lower rates on 

 Furthermore, large sample sizes are needed to compare adherence rates between specific agents, which may be driven by the balance between efficacy and tolerability. A previous large-scale pharmacy refill register study from 1998 to 1999 in (primarily male) military veterans with schizophrenia found that adherence was highest for 

 Whether adherence differs for newer oral antipsychotics or long-acting injectable (LAI) agents remains unclear.

Are you taking your medication? Researchers performed a nationwide register-based study of primary antipsychotic nonadherence in schizophrenia.

Schizophrenia/Psychosis