Antioxidant N-Acetylcysteine Improves Working Memory in Patients with Psychosis

June 20, 2018 · Posted in Potential Treatments · Comment 

NACIn a 2017 article in the journal Psychological Medicine, researcher Marta Rapado-Castro and colleagues reported that among 58 patients with bipolar disorder or schizophrenia and symptoms of psychosis, those who took two grams per day of the antioxidant n-acetylcysteine (NAC) showed improvements in working memory after six months compared to those who took placebo over the same study period.

Antipsychotic medications can typically reduce psychotic symptoms such as delusions or hallucinations, but cognitive symptoms such as problems with learning, memory, or information processing may remain. NAC, which is sold over-the-counter as a nutritional supplement, seemed to improve these symptoms.

The researchers suggest that larger studies of NAC are needed, particularly to determine whether giving NAC to patients during their first episode of psychosis could prevent cognitive decline from occurring at all during the course of their illness.

NAC has been found to have a range of benefits, including reducing substance abuse and interfering with habit-based behaviors such as compulsive hair-pulling, obsessive-compulsive disorder, and gambling.
Researcher Michael Berk, a co-author of the study, reported in the journal Biological Psychiatry in 2008 that NAC could also improve depressive symptoms in bipolar disorder and negative symptoms in schizophrenia.

Editor’s Note: Since cognitive deficits are common in both schizophrenia and bipolar disorder, using NAC in addition to antipsychotic medications could be a useful tool to address these types of symptoms.

Clinical Vignettes from Dr. Elizabeth Stuller

April 11, 2018 · Posted in Potential Treatments · Comment 

Dr. Elizabeth Stuller, a staff psychiatrist at the Amen clinics in Washington, DC and CEO of private practice Stuller Resettings in Baltimore, MD, provided this editor (Robert M. Post) with several interesting anecdotal observations based on her wide clinical experience with difficult-to-treat mood disordered patients.

  1. Stuller has used low-dose asenapine (Saphris), e.g. half a pill placed under the tongue, for depressed patients with alcohol use problems who have trouble getting to sleep. She has also used asenapine for rapid calming of agitated patients in her office.
  2. Stuller has also had success with the use of the atypical antipsychotic drug brexpiprazole (Rexulti) for patients with bipolar depression and low energy. She typically uses 0.5 mg/day for women and 1 mg/day for men. Stuller finds that there is little weight gain or akathisia with brexpiprazole.
  3. She has had success with the drug Nuedexta, which is a combination of dextromethorphan and quinidine and is approved for the treatment of sudden uncontrollable bouts of laughing or crying, known as pseudobulbar affect, which can occur as a result of neurological conditions or brain injuries. It is a combination of an NMDA antagonist and a sigma receptor agonist. Stuller starts with the 20mg dextromethorphan/10 mg quinidine dose once a day and increases to twice a day in week two. She finds it useful for behavioral effects of traumatic brain injury (TBI), anxiety resulting from the use of synthetic marijuana (sometimes called spice), and psychosis not otherwise specified. Stuller also finds that some patients appear to respond well to Nuedextra but not minocycline, or vice versa.

Editor’s Note: Note that these are preliminary clinical anecdotes conveyed in a personal communication, and have not been studied in clinical trials, thus should not be relied upon in the making of medical decisions. All decisions about treatment are the responsibility of a treating physician.

Antipsychotic Drug Pimavanserin Seems to Reduce Psychosis in People with Alzheimer’s

August 1, 2017 · Posted in Potential Treatments · Comment 

elderly womanThe antipsychotic drug pimavanserin was approved by the US Food and Drug Administration last year as a treatment for hallucinations and delusions in Parkinson’s disease. Now it looks as though it may also help people with Alzheimer’s disease. Pimavanserin works differently than other antipsychotic medications—a selective serotonin inverse agonist, it acts at serotonin HT2A receptors to produce effects opposite to those that serotonin would produce at the same receptor.

In a trial of 181 patients with Alzheimer’s and psychotic symptoms, those who received 34 mg/day of pimavanserin had a significant improvement in psychotic symptoms in six weeks compared to those who received placebo.

Over 12 weeks of treatment, pimavanserin did not impair cognition, as atypical antipsychotics can do.

Pimavanserin was well tolerated. The most common side effects were falls, urinary tract infections, and agitation. Like other atypical antipsychotics, the drug carries a box warning from the FDA that there is an increased risk of death when the drug is used to treat older people with dementia-related psychosis.

The FDA has designated pimavanserin a breakthrough therapy and is giving it priority review. These designations can speed up the development and review of a drug and are granted when a drug looks like it will be substantially better or safer than existing treatments for a serious condition.

Continuing Marijuana Use After a First Episode of Psychosis Increases Risk of Relapse

May 5, 2017 · Posted in Risk Factors · Comment 

marijuanaA 2016 article in the journal JAMA Psychiatry reports that continuing to use cannabis after a first episode of psychosis increases risk of relapse. The study by Sagnik Bhattacharyya and colleagues employed longitudinal modeling to determine the role of cannabis use in psychotic relapse. The researchers followed 90 women and 130 men for two years after a first episode of psychosis, and found that the more marijuana they used, the more likely they were to have a relapse of psychosis.

Relapse rates were highest (59.1%) for participants who used pot continuously following their first episode of psychosis. Relapse rates were lower (36.0%) for those who used cannabis intermittently thereafter, and lowest (28.5%) among those who discontinued cannabis use after their first episode of psychosis.

A statistical test known as a cross-lagged analysis was used to establish that cannabis use affected later relapse, rather than relapse of psychosis leading to further cannabis use.

Another statistical strategy using fixed-effect models revealed that risk of psychotic relapse was 13% higher during times of cannabis use than during periods of no cannabis use.

These findings offer some hope that the likelihood of psychosis relapse can be reduced, since ongoing cannabis use is a risk factor that can be modified, unlike family history or genetics. Bhattacharyya and colleagues called for research into interventions that can help discourage cannabis use in people who have had a first episode of psychosis.

Editor’s Note: N-acetylcysteine, a nutritional supplement sold in health food stores, can reduce cannabis use compared to placebo in teen users.

Early Cannabis Use and BDNF Gene Variant Increase Psychosis Risk

May 3, 2017 · Posted in Genetics, Risk Factors · Comment 

Teen smoking marijuanaNormal variations in genes can affect risk of mental illness. One gene that has been implicated in psychosis risk is known as BDNF. It controls production of brain-derived neurotrophic factor, a protein that protects neurons and is important for learning and memory. Another important gene is COMT, which controls production of the enzyme catechol-O-methyltransferase, which breaks down neurotransmitters such as dopamine in the brain.

Several forms of these genes appear in the population. These normal variations in genes are known as polymorphisms. Certain polymorphisms have been linked to disease risk. A study by Anna Mané and colleagues published in the Journal of Psychiatric Research in 2017 explored links between COMT and BDNF polymorphisms, cannabis use, and age at first episode of psychosis.

Mané and colleagues found that among 260 Caucasians being treated for a first episode of psychosis, the presence of a BDNF polymorphism known as val-66-met and a history of early cannabis use were associated with younger age at psychosis onset.

The val-66-met version of BDNF occurs in 25-35% of the population. It functions less efficiently than a version called val-66-val.

The researchers also found that males were more likely to have used cannabis at a young age.

Editor’s Note: In the general population, marijuana use doubles the risk of developing psychosis. Previous data had indicated that the risk was higher for those with a COMT polymorphism known as val-158-val that leads to more efficient metabolism of dopamine in the prefrontal cortex. The resulting deficits in dopamine increase vulnerability to psychosis compared to people with the val-158-met version of the COMT gene.

The new study by Mané and colleagues suggests that a common form of BDNF may be associated with an earlier onset of psychosis. Bottom line: Pot is dangerous for young users and can induce psychosis, particularly in people at genetic risk. Pot may be legal in many places, but heavy use in young people remains risky for mental health and cognitive functioning.

The company Genomind offers genetic testing for BDNF and COMT variants as part of a routine panel.

Cannabis Use May Cause Schizophrenia

May 1, 2017 · Posted in Risk Factors · Comment 

marijuanaCannabis use has been linked to schizophrenia risk, and new genetic research suggests a causal relationship between the two. In a 2017 article in the journal Molecular Psychiatry, researcher Julian Vaucher and colleagues reported that lifetime cannabis use was linked to schizophrenia even when the researchers controlled for 10 genotypes weakly associated with lifetime cannabis use. This makes it unlikely that the schizophrenia caused the cannabis use, suggesting instead that it is the cannabis use that leads to a schizophrenia diagnosis.

Vaucher and colleageus also controlled for genetic associations between cigarette smoking and cannabis use to eliminate cigarette use as a third variable causing the association between cannabis and schizophrenia.

The study by Vaucher and colleagues included 34,241 people with schizophrenia and 45,604 healthy controls.

Stimulants Linked to Psychotic Symptoms in Offspring of Parents with Psychiatric Illness

April 18, 2016 · Posted in Current Treatments, Risk Factors · Comment 

stimulants linked to psychotic symptoms

Stimulants are one of the most common medications prescribed to children and adolescents, typically for attention deficit hyperactivity disorder (ADHD). In children of parents with major depression, bipolar disorder, or schizophrenia, stimulant use may come with a risk of psychotic symptoms. A 2016 study by L.E. MacKenzie and colleagues in the journal Pediatrics reported that among children and youth whose parents had one of these psychiatric illnesses, 62.5% of those who had taken stimulants had current psychotic symptoms, compared to only 27.4% of those who had not taken stimulants. The participants with psychotic symptoms tended to have hallucinations that occurred while they were taking stimulants. Doctors may want to consider whether parents have a history of psychiatric illness when deciding whether to prescribe stimulants to children and adolescents with ADHD. Activation is a common side effect of antidepressants in children who have a parent with bipolar disorder. Young people taking stimulants for ADHD should be monitored for psychotic symptoms, particularly if they have a parent with a history of depression, bipolar disorder, or schizophrenia.

Omega-3 Fatty Acids Prevent Conversion to Psychosis

September 18, 2015 · Posted in Course of Illness, Current Treatments, Risk Factors · Comment 

omega-3 fatty acids for psychosis preventionA new long-term study of omega-3 polyunsaturated fatty acids for psychosis prevention shows that almost seven years after a 3-month stint of receiving these dietary supplements daily, adolescents and young adults at high risk for psychosis showed fewer symptoms of conversion to full-blown psychosis than those who received placebo during the same period.

The research team, led by Paul Amminger, originally found that among 81 youth (mean age 16.5) at high risk of developing psychosis due to their family histories, the 41 who received 12 weeks of daily supplementation with 700mg of eicosapentaenoic acid (EPA) omega-3s and 480 mg of docosahexaenoic acid (DHA) omega-3s showed reduced likelihood of conversion to psychosis one year later than the 40 who received placebo.

The team followed up an average of 6.7 years later with 71 of the original 81 participants. Among those who had received the omega-3 intervention, 9.8% had developed psychosis. Among the placebo group, 40% had developed psychosis, and they had done so earlier.

In addition, the omega-3 participants were better functioning, they had required less antipsychotic medication, and they had lower rates of any psychiatric disorder than the placebo group.
Amminger wrote in the journal Nature Communications, “Unlike antipsychotics, fish oil tablets have no side effects and arent’s stigmatizing to patients.”

Editor’s Note: Because of their lack of side effects, a good case can be made for omega-3 fatty acids for patients at high risk for psychosis. The novel thing about this study is that short-term treatment with omega-3 fatty acids had preventive effects almost 7 years later.

Specialty Treatment for First Episodes of Psychosis Effective

April 24, 2015 · Posted in Current Treatments · Comment 

collaborative care

A study published online in the journal Psychiatric Services comparing a specialty clinic that provides medication, family education, cognitive-behavioral therapy (CBT), and case management to improve employment and educational outcomes with treatment as usual for people in a first episode of psychosis found that the specialty treatment was associated with fewer and shorter hospital stays and better vocational engagement during one year of follow-up.

Most participants were referred to the study from inpatient psychiatric units. Those randomly assigned to receive treatment as usual typically did so in outpatient treatment settings. Those randomly assigned to the specialty treatment group joined the Specialized Treatment Early in Psychosis (STEP) program at the Connecticut Mental Health Center, where they could choose from any of the available interventions.

Other studies have found that comprehensive intervention encompassing psychoeducation, family therapy and other services can reduce psychotic symptoms. The authors of this study, Vinod H. Srihari and colleagues, concluded that a US public-sector model of early intervention in psychotic illness could be both feasible and effective.

Editor’s Note: In the British Journal of Psychiatry in 2013, Kessing et al. demonstrated even more dramatic and persistent benefits (for at least 6 years) of 2 years of specialty clinic care versus treatment as usual for patients with a first hospitalization for mania (many of whom were also psychotic). Together these two articles indicate the extreme importance of getting off to a good start in the management of major psychiatric illness. Such specialty programs are desperately needed for better management of childhood-onset mania.

N-acetylcysteine May Improve Prodromal Schizophrenia

September 16, 2014 · Posted in Potential Treatments · Comment 

NACAt the 2014 meeting of the International College of Neuropsychopharmacology, researcher N. Miyake described the effects of the nutritional supplement n-acetylcysteine (NAC) on clinical symptoms in subjects with subthreshold symptoms of psychosis.

N-acetylcysteine, a glutathione precursor, has neuroprotective effects. In this case series, four patients with subthreshold psychosis were given 2000mg/day of NAC for 12 weeks. The patients’ symptoms improved to the point that three of the four were no longer considered at risk for psychosis.

Editor’s Note: These promising anecdotal observations deserve careful follow up using a control group. Omega-3 fatty acids have been show to slow conversion to full psychosis and performed better than placebo in a controlled study. Both n-acetylcysteine and omega-3 fatty acids should definitely be studied for those with emerging symptoms of bipolar disorder.

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