Cannabidiol May Help Treat Schizophrenia

September 28, 2018 · Posted in Potential Treatments · Comment 

marijuanaA 2017 article by researcher Philip McGuire and colleagues in the American Journal of Psychiatry reports that when added to antipsychotic medication, cannabidiol, a component of marijuana, improved positive symptoms of schizophrenia, such as hallucinations and delusions, more than did the addition of a placebo.

In the double-blind, parallel-group study, 43 participants received 1000 mg/day of cannabidiol in addition to their regular antipsychotic medication, while 45 participants received a placebo alongside their regular medication.

Side effects were minimal, and after six weeks those who received cannabidiol had decreased positive symptoms and were more likely to be considered improved and not severely unwell.

Editor’s Note: It is important to emphasize that cannabidiol is only a minor component of marijuana, which contains much more tetrahydrocannabinol (THC), which is psycho-mimetic, i.e. it can worsen psychosis. Pure cannabidiol is not readily available to the public.

Withania Somnifera Herb Normalizes Sensory Processing Measure in Schizophrenia

September 26, 2018 · Posted in Potential Treatments · Comment 

One of the best biomarkers of schizophrenia is low auditory mismatch negativity. Auditory mismatch negativity describes the pattern of electrical activity that occurs in the brain when a repeated sound is interrupted by a mismatched sound, such as a change in pitch or volume.

At the International Congress on Schizophrenia Research, Paulina S. Marell and colleagues described their pilot study of the antioxidant and anti-inflammatory herb Ashwagandha or Withania Somnifera (also known as Indian ginseng, poison gooseberry, or winter cherry). In 11 patients with schizophrenia, the herb normalized mismatch negativity compared to placebo.

Marell and colleagues wrote that the herb “recover[ed] some of the impaired early sensory/cognitive potentials in schizophrenia.” Since normal cognition relies on sensory processing, normalizing these functions in people with schizophrenia could improve their symptoms.

A 2018 study by researcher K.N. Roy Chengappa and colleagues in the Journal of Clinical Psychiatry reports that adding Withania Somnifera to patients’ regular antipsychotic medication improved negative symptoms of schizophrenia and total symptoms compared to adding placebo.

Editor’s Note: These studies, taken together, suggest the utility of adding this supplement to the treatment regimen for schizophrenia.

Sodium Benzoate Helps Treat Schizophrenia When Added to Clozapine

September 24, 2018 · Posted in Potential Treatments · Comment 

schizophrenia

In a 2017 article in the journal Biological Psychiatry, Chieh-Hsin Lin and colleagues reported that sodium benzoate, a common food preservative, may augment the effects of clozapine in patients with schizophrenia.

Clozapine is the most effective antipsychotic available, but as many as 40–70% of patients with treatment-resistant schizophrenia do not respond to it. For those with a poor response to clozapine, sodium benzoate may offer some hope.

In a randomized, double-blind trial, sixty inpatients taking clozapine for schizophrenia were divided into three groups. One group received an additional 1 g/day of sodium benzoate, another received 2 g/day, and the third received placebo in addition to clozapine. Both groups taking sodium benzoate and clozapine showed improvements in negative symptoms of schizophrenia (which can include apathy and inability to experience pleasure) compared to the group taking only clozapine. The larger 2g dose also improved positive symptoms of schizophrenia (such as hallucinations or delusions) and quality of life. Changes in levels of the antioxidant catalase were linked to the total improvement in symptoms and the improvement in positive symptoms. Sodium benzoate did not seem to cause any side effects.

Editor’s Note: Sodium benzoate is a D-amino acid oxidase inhibitor that activates NMDA receptors and increases levels of the amino acid D-serine in the brain by preventing it from breaking down. D-serine can reverse the effects of the illicit drug PCP, and very high doses of D-serine have improved the effectiveness of atypical antipsychotics in people with schizophrenia. By increasing levels of D-serine, sodium benzoate may offer new benefits to people with schizophrenia, especially those who have not responded to other treatments.

Single Dose of Ketamine Reduces Suicidal Ideation

September 18, 2018 · Posted in Potential Treatments · Comment 

Nurse Giving Patient Injection

A systematic review and meta-analysis by Samuel T. Wilkinson and colleagues in the American Journal of Psychiatry analyzed individual patient data from 10 studies in which a single intravenous dose of ketamine was given to patients with suicidal ideation. The review included data from a total of 167 participants.

Wilkinson and colleagues found that ketamine reduced suicidal ideation within 24 hours, and these effects lasted for up to seven days. Mood also improved, but the reduction in suicidal ideation was independent of the degree of improvement in depression.

Among the participants, 54.9% were free of suicidal ideation at 24 hours after the infusion, 60.0% were free of suicidal ideation one week after the infusion, and 61.1% were free of suicidal ideation at two weeks.

Editor’s Note: The authors report that there is much to clarify about ketamine treatment before it can be used clinically to treat patients at risk for suicide. However, ketamine’s powerful and rapid effects offer an interesting alternative to other slow-acting treatment options, and could be an ideal acute treatment for patients arriving in an emergency room because of high suicide risk. A ketamine injection could be especially useful  for those who are not admitted to the hospital, as it could produce anti-suicidal effects that could help carry a patient over until their next psychiatric appointment.

Mixed Findings for Intranasal Ketamine

September 13, 2018 · Posted in Potential Treatments · Comment 

intranasal ketamine

The drug ketamine can rapidly and temporarily improve depression when delivered intravenously. Researchers have been working on extending ketamine’s effects and finding easier ways of delivering the medication. One new delivery method under investigation is nasal spray, which could be used repeatedly to extend ketamine’s effects.

Unfortunately, researcher Colleen Loo reported in the Journal of Psychopharmacology in 2018 that a pilot study of self-administered intranasal ketamine for severe depression was suspended when 5 of the 10 participants had side effects that included high blood pressure, psychotic symptoms, and motor incoordination that made them unable to keep using the spray. Early in the four-week study, dosage was adjusted to leave more time between sprays, but this was not enough to prevent the problems with side effects.

Loo said that the nasal spray version of ketamine has complications including variations in absorption among different people and on different days, depending on factors like mucus in the nose and exact application techniques. Its rapid absorption into the bloodstream could lead to high peak levels in certain people.

Loo and colleagues had previously found that elderly patients receiving injections of ketamine under the skin required highly individualized dosing to avoid side effects. This may also be the case with nasal spray.

While Loo’s study found intranasal ketamine infeasible for the moment, Janssen Research and Development, a pharmaceutical company owned by Johnson & Johnson, reported positive results in phase 3 clinical trials of intranasal esketamine (a component of ketamine) at the annual meeting of the American Psychiatric Association in May. Researchers for Janssen reported that intranasal esketamine was highly effective for depression and well-tolerated both in acute treatment and over a year-long period. Janssen is now pursing approval for the drug from the US Food and Drug Administration.

 

Repeated Ketamine Reduces PTSD and Depression in the Short Term

September 11, 2018 · Posted in Comorbidities, Potential Treatments · Comment 

iv ketamine

In a 2018 open study by C. Sophia Albott and colleagues in the Journal of Clinical Psychiatry, veterans with post-traumatic stress disorder (PTSD) and a simultaneous diagnosis of major depression were treated with six infusions of intravenous ketamine over a 12-day period (Mondays, Wednesdays, and Fridays for two weeks).

Ketamine produced large improvements in both conditions. The remission rate was 80.0% for PTSD and 93.3% for depression. The median time to first relapse after the treatment was 41 days for PTSD and 20 days for depression.

One side effect of ketamine was that dissociative symptoms increased temporarily with repeated infusions. PTSD symptoms did not worsen among those participants taking ketamine.

The study was intended to evaluate the efficacy, safety, and durability of repeated ketamine infusions. Ketamine has been used in emergency rooms to rapidly treat depression and suicidality, but the effects of a single infusion fade within days.  Albott and colleagues reported that this treatment scenario with multiple ketamine infusions produced rapid results that lasted longer than single ketamine infusions.

Editor’s Note: While this study found that repeated ketamine infusions were safe, it is possible that long-term use may lead to addiction. Researcher Nolan R. Williams and colleagues reported in a 2018 article in the American Journal of Psychiatry that ketamine works via activation of the opiate receptor.  The drug naloxone, which rapidly reverses opiate overdose, completely blocked ketamine’s antidepressant effects.

 

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.

Specific Probiotics Reduce Re-Hospitalizations for Bipolar Disorder

June 7, 2018 · Posted in Potential Treatments · Comment 

taking pill

In a 2018 article published in the journal Bipolar Disorders, researcher Faith Dickerson and colleagues reported that in a small study of 66 people who had been hospitalized for mania, taking specific probiotic supplements upon their release reduced re-hospitalizations compared to taking placebo.

The study followed patients for 24 weeks after their hospitalization. They were randomized to receive either the combination of Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12 or placebo in addition to their regular medications. While 17 of the 33 participants in the placebo group (51.5%) had at least one re-hospitalization during the study period, only eight (24.2%) of the participants taking probiotics had a re-hospitalization. The duration of the re-hospitalizations was also shorter for those taking probiotics (2.8 days on average versus 8.3 days for those taking placebo).

In a personal communication to this editor (Robert M. Post), Chris Aiken, Instructor in Clinical Psychiatry at Wake Forest University School of Medicine, who was not involved in the study, provided some clarifying details to this editor about the use of probiotics to reduce manic relapse. Aiken explained, “Apparently, it’s important to get both the right species (e.g. Bifidobacterium lactis) and the right strain (e.g. Bb-12) in choosing a probiotic. The study mentions that one of the strains (Bb-12) is patented and only available in Europe, but it has been licensed to a few U.S. companies.

“I found two products that contain the exact strains in the study and wrote this up for patients: In [the] study [noted above], a probiotic capsule containing Bifidobacterium lactis Bb-12 and Lactobacillus rhamnosus GG lowered the risk of psychiatric hospitalization threefold. [Both] strains are available in the supplement Emergen-C and in a liquid probiotic designed for infants, Culturelle Baby Grow and Thrive. The infant serving would suffice for adults as well. You could also get the two strains by combining two separate probiotic capsules: Align Daily Immune Support and Culturelle Digestive Health Daily Priobiotic.”

Editor’s Note: We are grateful to Dr. Aiken for this added information. We also found that USANA probiotic also contains both strains used in the study. Recent research has found more and more connections between inflammatory processes and mental health. This study contributes to our understanding of the connection between gut health and the brain.

NAD Precursor May Improve Cardiovascular Health

June 5, 2018 · Posted in Potential Treatments · Comment 

heartNAD, or nicotinamide adenine dinucleotide, is found in all living cells. Its oxidized form, NAD+, rose in popularity as a nutritional supplement following a 2013 Harvard study that suggested it might slow aging in mice. A 2018 article by researcher Christopher R. Martens and colleagues in the journal Nature Communications reports that a precursor vitamin to NAD+ called nicotinamide riboside (NR) can stimulate NAD+ metabolism in healthy middle-aged and older adults compared to placebo, which might improve cardiovascular health. In the crossover study, participants received NR or placebo for six weeks, and then received the other option for a second six-week period. NR was associated with increased NAD+ metabolism.

The researchers suggest that more research is needed to investigate whether chronic NR supplementation might be able to reduce blood pressure and arterial stiffness.

Third Study Suggests Cariprazine Is Effective in Bipolar Depression

June 2, 2018 · Posted in Current Treatments, Potential Treatments · Comment 

cariprazine

The atypical antipsychotic drug cariprazine (sold under the name Vraylar in the US) is currently approved by the US Food and Drug Administration for the treatment of schizophrenia and manic or mixed episodes of bipolar disorder. Based on recent successful phase 3 trials in bipolar depression, the pharmaceutical companies that produce cariprazine, Allergan and Gedeon Richter, plan to apply for a change in FDA labeling later this year to reflect the drug’s apparent ability to treat bipolar depression as well.

While many drugs can prevent or treat mania, treating bipolar depression has typically been more of a challenge. The most recent 6-week trial of cariprazine in 493 patients showed that a dose 1.5mg/day was significantly more effective than placebo at reducing depression ratings. (A dose of 3mg/day did not show superiority over placebo as it had in previous trials of cariprazine.)

Side effects reported in the trial were mild and included restless legs, nausea, and fatigue. Five percent of those who received cariprazine discontinued the drug due to side effects, compared to three percent of those who received placebo.

The mechanism by which cariprazine improves depression is not yet clear. The drug is a dopamine partial agonist, but unlike aripiprazole (Abilify) and brexpiprazole (Rexulti), which have more potent effects on D2 receptors than on D3 receptors, cariprazine is more potent at dopamine D3 receptors. Whether this difference accounts for the positive effects in bipolar depression that aripiprazole and brexpiprazole do not have remains to be seen.

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