Supplements for the Treatment of Schizophrenia

November 16, 2018 · Posted in Potential Treatments · Comment 

supplements

At the 2018 meeting of the North Carolina Psychiatric Association, researcher Karen Graham reviewed evidence for adjunctive treatments that may help treat schizophrenia when added to antipsychotic medications.

Graham endorsed omega-3-fatty acids, saying that they may delay the conversion to schizophrenia in young people at high risk for the illness. Data in chronic schizophrenia are more equivocal.

Data on the effects of vitamin D3 in schizophrenia are mixed, but D3 is often low in patients with psychotic disorders, and supplementation with vitamin D3 in the general population has been associated with decreases in cancer and all-cause mortality.

Graham indicated that in three studies vitamin B6 (pyridoxine) decreased tardive dyskinesia, a side effect of antipsychotic medication that is characterized by repetitive or jerky involuntary movements of the face and body. B6 also reduced the severity of akathisia or restless legs, which is comparable to the effects of 40mg/day of the beta blocker drug propranolol. Graham recommended a dose of 300mg/day of B6 that could be increased up to 600mg twice per day. The onset of effects usually begins by week three, and the cost ranges from 25 to 80 cents per day.

The antioxidant supplement N-acetylcysteine (NAC) may also help. Graham described six studies that found NAC had positive effects on negative symptoms (apathy, blunted emotions, etc.) and/or cognition in patients with schizophrenia. The dosage in these studies was usually 2 grams/day for 24 weeks. The cost was 50 cents per day.

Two 8-week trials of L-theanine (an amino acid found in green and black tea) at doses of 400mg/day improved negative symptoms and anxiety in 40 patients with schizophrenia. The rationale for the study was that L-theanine increases inhibitory neurotransmitters, modulates the amino acid 5-HTP and the neurotransmitter dopamine, increases brain-derived neurotrophic factor (BDNF), and may be neuroprotective after a heart attack or a traumatic brain injury. The cost is 40 cents per day.

Graham reported that the supplement ginkgo biloba produced significant improvement in negative symptoms and total symptoms in eight clinical trials that included a total of 1,033 patients with schizophrenia. Doses ranged from 240 to 360 mg/day. These supplements (usually extracted from leaves of the ginkgo tree) have not been found to have many side effects, but they can reportedly increase post-operative bleeding. Gingko biloba supplements cost 20 to 80 cents per day. There is also at least one positive study of ginkgo biloba in tardive dyskinesia.

Three of four studies of cannabidiol in schizophrenia have been positive (at doses of 600, 800, and 1,000 mg/day in studies that lasted four to six weeks). There are now six additional ongoing studies listed on the website clinicaltrials.gov. There is little of this diol component in regular marijuana, and the cost of pure cannabidiol is unfortunately an exorbitant $60 to $100/day.

There is a positive controlled study of the herb ashwagandha in 66 patients with schizophrenia.

Not included in Dr. Graham’s review was the prenatal treatment of women with phosphatidylcholine (900mg/day) followed by supplements in the newborn, which normalized an aspect of sensory gating known as P50 in patients with schizophrenia. Healthy individuals show a reduced response to an auditory cue when it is repeated 50 milliseconds after the initial cue. In people with schizophrenia, response to the repeated cue is not suppressed. This has been suggested by researchers Robert Freedman and Randal G. Ross in a 2015 article in the Shanghai Archives of Psychiatry as a possible primary preventive approach to schizophrenia.

Pregnant women in their second and third trimesters should at least consume foods high in choline, especially if the fetus is at high risk for schizophrenia because of a family history of schizophrenia.

Beef liver is very high in choline, providing 420mg per slice. Other animal products provide significant choline, such as eggs (120 mg/egg), beef (90mg/100g), chicken liver (85mg/liver), fish (85mg/100g), bacon (35mg/strip) or other pork, chicken (67mg/100g). Tofu (36mg/half cup) and cereal (22mg/half cup) are also sources of choline.

Foods High in Choline

Beef liver 1 slice 420mg choline;
Egg 1 egg 120;
Beef 100 gm 90;
Chicken liver 1 liver 85;
Fish 100 gm 85;
Bacon or pork 2 strips bacon 70;
Chicken 100 gm 67;
Tofu 120 ml (0.5 cup) 36;
Cereal 120 ml (0.5 cup) 22

 

Early Intervention Works in Schizophrenia: Also Needed in Bipolar Disorder

October 4, 2018 · Posted in Current Treatments, Peer-Reviewed Published Data · Comment 

man

For twenty years, evidence has shown that early intervention can ameliorate many of the adverse consequences of schizophrenia. In a 2018 article in the journal Annual Review of Clinical Psychiatry titled “Transforming the treatment of schizophrenia in the United States: The RAISE Initiative,” Lisa B. Dixon and colleagues described the importance of early intervention in schizophrenia. RAISE stands for Recovery After an Initial Schizophrenia Episode. Dixon and colleagues emphasize that shortening the time that a patient’s psychosis goes untreated, which averages 74 months, is critical to achieving good outcomes. In parallel to these consistent findings, researchers of bipolar disorder (including this editor Robert M. Post and colleagues) have found that an increased length of the interval before treatment is initiated in childhood-onset bipolar disorder is associated with a poor outcome in adulthood.

The RAISE program consists of four interventions: personalized psychopharmacology using a computerized decision support system, individual resilience therapy, family psychoeducation and therapy, and supportive employment and education. Compared with patients receiving standard treatments, patients who participated in the RAISE program showed greater improvements on almost all measures, including the Heinrichs-Carpenter Quality of Life Scale (main outcome), the Calgary Depression Scale for Schizophrenia, the Positive and Negative Syndrome Scale, treatment duration, and engagement in work and school. Moreover, the improvements were more substantial among patients with a shorter duration of untreated psychosis.

Editor’s Note: These findings are of great importance in their own right, but they also have great implications for treatment and research efforts in bipolar disorder. A 2013 randomized study by Lars Kessing and colleagues published in the British Journal of Psychiatry found that in bipolar patients hospitalized for a first or second episode of mania, two years of comprehensive treatment with psychotherapy, pharmacotherapy, and illness education that included mood monitoring and early symptom recognition was vastly superior to typical treatment, and this held true even six years later. In a 2014 article in the Journal of Clinical Psychiatry and a 2016 article in the journal Bipolar Disorders, researcher Jan Marie Kozicky and colleagues reported that in patients hospitalized with a first episode of mania, cognitive functioning and brain imaging abnormalities, respectively, returned to normal over the next year only if the patients experienced no further mood episodes. The message is clear: we must treat the first episode of mania comprehensively to avoid long-term deterioration, which occurs as a function of the number of episodes of mania or depression a patient experiences. However, this early multimodal approach is rarely taken in the US.

In schizophrenia, Dixon and colleagues noted that: “After the RAISE study reports were made available, Congress allocated additional funding to the community mental health …program, leading to growth in the number of…programs across the United States; they were expected to reach 48 states in 2018.”

The contrast between these efforts in schizophrenia and their virtual absence in bipolar disorder is incomprehensible and tragic. Studies in early schizophrenia have been funded for 25 years, while almost none have been funded in bipolar disorder, even in recent years. Community mental health programs for early schizophrenia will soon exist in 48 states; for patients with bipolar disorder there are no programs available in any state that I am aware of. The incidence of bipolar is about three times that of schizophrenia, and the long-term outcomes are often as devastating in bipolar disorder as in schizophrenia. There is a high incidence of drug abuse; social, educational and occupational deficits; and suicide in bipolar disorder. Early intervention with the many safe supplements, nutraceuticals, and well-tolerated drugs that are currently available to adult patients should be studied in young people with bipolar disorder, but such studies neither being funded nor conducted.

The reality is that childhood-onset bipolar disorder is poorly recognized and treated in the US, largely because of a paucity of treatment-related studies and knowledge about the best options for these young patients. If a reader of the BNN knows how to influence advocacy groups, leaders in the Substance Abuse Mental Health Services Administration (SAMHSA) and the National Institutes of Mental Health (NIMH), or influential politicians, it would be useful to take the initiative in bringing some of these deficits and disparities to their attention. Something must be done; ideas about how to do it are welcome. My own efforts to get funding for a childhood-onset bipolar research network in collaboration with such luminaries in the field as David Miklowitz (UCLA), Kiki D. Chang (Stanford University), Boris Birmaher (University of Pittsburg), Benjamin Goldstein (Stonybrook Research Institute), Eric Youngstrom (UNC, Chapel Hill), Soledad Romero (Hospital Clinic of Barcelona), and Josefina Castro Fornieles (University of Barcelona) have not been successful. We will keep trying, but the field needs to reach beyond the many investigators who are advocating for more treatment research to other people with more influence.

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.

Early Intervention Improves Outcomes in Early-Stage Schizophrenia

 

doctor with teen boy

A recent meta-analysis of 10 studies found that early intervention after a first episode of psychosis or in the early stages of a schizophrenia spectrum disorder led to better patient outcomes than treatment as usual.
The meta-analysis by researcher Christoph U. Correll and colleagues appeared in the journal JAMA Psychiatry in 2018. The 10 studies that were included had randomized a total of 2,176 patients to receive either treatment as usual or early intervention services, which typically include efforts at early detection of symptoms, early treatment with low doses of antipsychotic medication, interventions to prevent relapse, and strategies to help patients return to normal work and social activities.

Those patients who received early intervention services were less likely to discontinue treatment, were less likely to have a psychiatric hospitalization, were more involved in school or work, and had less severe symptoms, including both positive and negative symptoms of schizophrenia.

The authors called for better funding and implementation of early intervention services in early psychosis or the beginning stages of schizophrenia.

Editor’s Note: This finding with regard to schizophrenia spectrum disorders emphasizes the enormous disparity in allocation of research resources for the study of early psychosis versus early bipolar disorder, where almost no studies of this kind have been done.

The mean age of the patients in this psychosis meta-analysis was 27.5 years. Symptoms of bipolar disorder can often begin earlier, in childhood, and early onset of bipolar disorder predicts poor long-term outcomes into adulthood and is associated with a high risk of substance abuse and suicide. This editor (Robert M. Post) and many colleagues have witnessed two decades of scientific literature on early-onset bipolar disorder. We know that early intervention is necessary, but more treatment studies are needed at the early stages of the illness, and calls for funding treatment-focused research have gone unheeded.

More advocacy is needed among families affected by bipolar disorder and advocacy groups interested in better treatment of bipolar disorder. We must try to change the abysmal status quo and campaign publicly, privately, and politically for more funds and public health attention to be directed toward early intervention in bipolar disorder.

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.

Simvastatin Looks Promising in Treatment of Negative Symptoms of Schizophrenia

December 20, 2017 · Posted in Potential Treatments · Comment 

simvastatin

The statin drug simvastatin (Zocor) enhances the effects of risperidone on negative symptoms of schizophrenia, according to a 2017 article by Soode Tajik-Esmaeeli and colleagues in the journal International Clinical Psychopharmacology.

In the 8-week study, 40 mg/day of simvastatin enhanced the effects of 4–6 mg/day of the antipsychotic risperidone on negative symptoms of schizophrenia, such as apathy and withdrawal, but not positive symptoms such as hallucinations or delusions.

Other statins, lovastatin and pravastatin, have not had a similar effect, possibly because they do not cross the blood-brain barrier as easily as simvastatin does.

Simvastatin has other benefits as well. Like all statins it decreases lipid levels, reducing cardiovascular disease. People with schizophrenia and bipolar disorder are at especially high risk for cardiovascular disease.

Simvastatin also decreases inflammation (lowering IL-1 alpha and TNF-beta levels) and may be neuroprotective, as it increases brain-derived neurotrophic factor (BDNF), a protein that protects neurons and is important for learning and memory. Inflammation is increasingly implicated in schizophrenia and bipolar disorder.

There is also some evidence that statins can prevent depressions over long-term follow-up. Studies in women without depression and men who had recently had heart attacks both showed that those taking statins had a lower rate of future depression than those not taking statins.

Editor’s Note: These findings suggest a potential 5-fold benefit to simvastatin: 1) It reduces negative symptoms in schizophrenia. 2) It reduces inflammation. 3) It increases BDNF. 4) It decreases cardiovascular disease risk by lowering lipid levels. 5) It may prevent future depressions.

Other approaches to augmenting schizophrenia treatment include nutritional supplements vitamin D3 and folate. Patients with psychosis often have vitamin D deficits. Folate supplements can reduce homocysteine, which has been linked to cognitive deficits in schizophrenia.

Liraglutide Decreased Body Weight, Improved Glucose Tolerance and Cardio Health in Schizophrenia

December 18, 2017 · Posted in Potential Treatments · Comment 

weightA 2017 article by Julie R. Larsen and colleagues in the journal Archives of General Psychiatry reported that the drug liraglutide, a treatment for type 2 diabetes, improved certain health measures in people with schizophrenia who were overweight and prediabetic and being treated with the atypical antipsychotics olanzepine or clozapine.

In the 16-week trial, patients received a daily 2 mg injection of liraglutide under the skin or placebo. Liraglutide decreased body weight, improved glucose tolerance, and improved cardio-metabolic measures. Weight decreased by more than 10 pounds on average compared to placebo.

Liraglutide is derived from a human metabolic hormone. It binds to the same receptors as does the metabolic hormone GLP-1, which stimulates insulin secretion.

FDA Approves New Higher Dose of Valbenazine for Tardive Dyskinesia

December 15, 2017 · Posted in Current Treatments · Comment 

tardive dyskinesia

The US Food and Drug Administration has approved an 80 mg capsule dose of valbenazine (Ingrezza) for tardive dyskinesia (jerky, involuntary movements of the face, especially the mouth and tongue, fingers and body that can be a side effect of antipsychotic medication). Valbenazine, a selective vesicular monoamine transporter 2 inhibitor, was the first drug FDA-approved for tardive dyskinesia. The FDA initially approved a dosage of 40 mg/day in April 2017. The 80 mg/day dose was approved in October 2017.

The new approval was based on a 6-week clinical trial in which 80 mg of valbenazine improved tardive dyskinesia significantly compared to placebo. Improvement continued over 48 weeks of treatment.

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