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

 

Omega-3 Fatty Acids Improve Executive Function in Youth with Mood Disorders

January 29, 2018 · Posted in Current Treatments · Comment 

omega-3 fatty acids

A 2017 study by Anthony T. Vesco and colleagues in The Journal of Child Psychology and Psychiatry suggests that in youth with depression or bipolar not otherwise specified (BP-NOS), omega-3 fatty acid supplements improve executive functioning and behavior regulation compared to placebo.

Ninety-five participants aged 7–14 years received two capsules daily of either omega-3 fatty acids (1.87g total per day, mostly consisting of EPA) or placebo for 12 weeks. Those who received omega-3s showed improvement in executive functioning (which can include planning and decision-making), behavioral regulation, and metacognition, as rated by their parents.

Editor’s Note: Since omega-3 fatty acids have no known side effects, there is little reason not to try them in youth with depression or bipolar disorder.

Omega-3 Fatty Acids Improve ADHD

January 26, 2018 · Posted in Current Treatments · Comment 

sources of omega-3 fatty acidsA 2017 systematic review and meta-analysis found that omega-3 fatty acid supplementation improves symptoms of attention-deficit hyperactivity disorder (ADHD) in children and adolescents. The article by Jane Pei-Chen Chang and colleagues in the journal Neuropsychopharmacology identified seven randomized controlled trials in which omega-3 fatty acids improved clinical symptoms of ADHD, and three trials in which omega-3s improved cognitive measures associated with attention.

The meta-analysis also found that children and adolescents with ADHD have lower than normal levels of the omega-3s DHA and EPA, in addition to lower total levels of omega-3s measured in blood and cheek tissues.

Chang and colleagues suggest that omega-3 fatty acid supplementation is a potentially helpful and largely risk-free treatment option for ADHD in children and adolescents.

Omega-3 Fatty Acids May Be Helpful Early in Schizophrenia, But Not Later

January 24, 2017 · Posted in Potential Treatments · Comment 

sources of omega-3 fatty acidsSome studies have suggested that omega-3 fatty acids may be helpful in the treatment of schizophrenia, but data to support this idea have been inconsistent. A recent meta-analysis of research on omega-3s and schizophrenia suggests that this nutritional supplement might be more useful in early-stage schizophrenia than in later illness.

At the 2016 meeting of the Society of Biological Psychiatry, researchers led by Alexander T. Chen presented the findings of their meta-analysis. First they analyzed six studies that shared a common scale for measuring schizophrenia symptoms. In these studies, omega-3 fatty acids did not outperform placebo when used as an add-on treatment to antipsychotics for people with schizophrenia.

In four remaining studies of omega-3 fatty acids and schizophrenia, the omega-3s were associated with improvement only in patients in the early stages of schizophrenia. Compared to placebo, the supplements decreased non-psychotic symptoms, decreased the dosage of antipsychotic medication patients required, and improved early treatment response (but not late treatment response) in patients in their first episode of schizophrenia.

In the same study, omega-3 fatty acids also reduced conversion to full-blown schizophrenia and psychotic symptom severity in patients at high risk for schizophrenia who were having preliminary symptoms of the illness.

Editor’s Note: Researcher Paul E. Keck has also found that omega-3 fatty acids may be more effective early in bipolar disorder rather than later. He reported that younger patients with bipolar depression and rapid cycling showed more improvement when taking the omega-3 fatty acid EPA than when taking placebo. In contrast, patients with bipolar depression who were over the age of 45 did worse on EPA than on placebo.

Part of the ambiguity about whether omega-3 fatty acids can help treat or prevent mental illness may be explained by the supplements working better in younger people or earlier in the course of an illness.

Meta-Analysis Shows Anti-Inflammatory Treatments Improve Bipolar Depression

November 22, 2016 · Posted in Current Treatments · Comment 

anti inflammatory treatments for bipolar depressionIt has been clear for some time that depression and inflammation are linked. This has led researchers to explore a variety of anti-inflammatory agents to treat depression. A meta-analysis of studies examining anti-inflammatory treatments for bipolar depression was published in the journal Bipolar Disorders in 2016.

Researcher Joshua D. Rosenblat and colleagues identified eight randomized controlled trials that met their criteria for anti-inflammatory treatments of bipolar disorder. These treatments included nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen and aspirin), omega-3 fatty acids, the antioxidant N-acetylcysteine, and pioglitazone (used to treat diabetes). Overall, the anti-inflammatory treatments had a moderate and statistically significant antidepressant effects. No serious side effects were reported, and the anti-inflammatory treatments did not cause a switch into mania in any of the participants.

The diversity of the anti-inflammatory treatments reviewed in this meta-analysis limit the extent to which it can be interpreted, but it is clear that more research on anti-inflammatory treatments for bipolar depression is needed. An open question is whether patients with particularly elevated levels of inflammatory markers in their blood would respond better to these anti-inflammatory treatments.

Certain ‘Nutraceuticals’ Aid Depression Treatment

October 31, 2016 · Posted in Potential Treatments · Comment 

nutraceuticals

A systematic review of research on the value of pharmaceutical-grade nutritional supplements, or ‘nutraceuticals,’ in depression treatment has found that several do indeed improve depression symptoms.

The 2016 review by Jerome Sarris and colleagues in the American Journal of Psychiatry found that the following nutraceuticals primarily produced positive results compared to placebo: omega-3 fatty acids (primarily EPA or ethyl-EPA); vitamin D; l-methylfolate (a more potent form of folic acid); and S-adenosyl methionine or SAMe, a beneficial compound created from toxic homocysteine with the help of folate.

Editor’s Note: Most of these compounds can also be useful in bipolar depression. Omega-3 fatty acids and vitamin D are helpful to many patients. L-methylfolate is particularly helpful to the 30% of the population with a MTHFR deficiency that interferes with the ability of folate to break down homocysteine. SAMe is an exception—while it is effective in unipolar depression, it may cause switching into mania in patients with bipolar disorder.

The researchers identified a few additional nutraceuticals that each had one study supporting their use—creatine, sometimes used by weightlifters to provide extra energy to muscles; folinic acid, which can protect bone marrow and other cells during chemotherapy; and a combination of amino acids.

Results from studies that compared other compounds to placebo were mixed. Those included studies of zinc, folic acid, vitamin C, and the amino acid tryptophan. A study of inositol, a compound found in plants that is not normally digestible, had nonsignificant results.

No serious side effects were observed in any of the studies of nutraceuticals, though some caused minor digestive disturbances.

Editor’s Note: Another beneficial nutraceutical that did not appear in the review article is N-acetylcysteine. In 6- to 8-week studies, NAC improved depression and anxiety compared to placebo. It also improved bipolar depression and reduced many habits and additions in non-bipolar patients. These include cocaine and gambling addition, alcohol and nicotine use, trichotillomania (compulsive hair-pulling) and obsessive compulsive disorder (OCD).

Omega-3 Fatty Acids Associated with Small Improvement in Depression in Children Aged 7–14

February 22, 2016 · Posted in Potential Treatments · Comment 

omega 3s

At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Mary A. Fristad reported that omega-3 fatty acid supplements had a small beneficial effect on depression in children aged 7–14. The supplements did not noticeably improve bipolar disorder not otherwise specified (NOS) or mania. The supplements consisted of several types of omega-3 fatty acids, including 1400mg of EPA, 200mg of DHA, and 400mg of others per day. The children were also undergoing psychotherapy during the study.

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.

People with High Inflammation Respond Best to EPA Omega-3 Fatty Acids in Depression

May 13, 2015 · Posted in Current Treatments · Comment 

omega-3 fatty acids for depression

Omega-3 fatty acids are found in some green vegetables, vegetable oils, and fatty fish. There is some evidence that omega-3 fatty acid supplements can reduce depression, but researchers are trying to clarify which omega-3s are most helpful, and for whom. A new study in Molecular Psychiatry suggests that depressed people with higher inflammation may respond best to EPA omega-3 fatty acids compared to DHA omega-3 fatty acids or placebo. Researchers led by M.H. Rapaport divided people with major depressive disorder into “high” and “low” inflammation groups based on their levels of the inflammatory markers IL-1ra, IL-6, high-sensitivity C-reactive protein, leptin, and adiponectin. Participants were randomized to receive eight weeks of treatment with EPA omega-3 supplements (1060mg/day), DHA omega-3 supplements (900mg/day), or placebo.

While overall treatment differences among the three groups as a whole were negligible, the high inflammation group improved more on EPA than on placebo or DHA, and more on placebo than on DHA. The authors suggest that EPA supplementation may help relieve symptoms of depression in people whose depression is associated with high inflammation levels, a link common among obese people with depression.

Editor’s Note: These data add to a study by Rudolph Uher et al. in which people with high levels of C-reactive protein responded better to the tricyclic antidepressant nortriptylene, while those with low levels of the inflammatory marker responded better to the selective serotonin reuptake inhibitor antidepressant escitalopram.

Omega-3 Fatty Acids Improve Attention in Boys

May 11, 2015 · Posted in Current Treatments · Comment 

Margarine with omega-3s

A new study finds that omega-3 fatty acid supplementation improves attention in boys both with and without attention deficit hyperactivity disorder (ADHD). The study by Dienke J. Bos and colleagues in the journal Neuropsychopharmacology included 40 boys (aged 8–14) with ADHD and 39 demographically matched controls. Participants were given 10 g per day of margarine supplemented with either omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) or placebo.

The children who received EPA/DHA supplementation showed improvements in attention (as rated by parents) compared to those who received placebo. Improvement was greater in the children with ADHD. Supplementation did not affect cognitive control or brain activity on functional magnetic resonance imaging (fMRI). Those boys who received omega-3s showed higher DHA levels on followup.

 

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