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.
A 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.
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.
At 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.
A 2014 study by Sarah E. Canetta et al. in the American Journal of Psychiatry suggests that children whose mothers had influenza during pregnancy are at higher risk for bipolar disorder with psychotic features. The same researchers had previously found that maternal influenza during pregnancy increased a child’s risk of developing schizophrenia, suggesting that there is a link between maternal influenza and psychotic symptoms in the offspring.
In the current study, influenza infections were identified by measuring levels of flu antibodies in blood. In a previous study, participants were considered to have influenza if they had been diagnosed clinically. Possibly due to this difference, that study showed a link between maternal flu infections and bipolar disorder in general (not just psychotic cases).
At the 2012 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), Carrie E. Bearden presented data from a study that predicted conversion to psychosis in at-risk youth (those who have prodromal symptoms or a particular genetic mutation that leads to psychosis) by observing white matter abnormalities.
Bearden found that the degree of white matter abnormality seen during magnetic resonance imaging (MRI) was proportional to the degree of cognitive deficit in patients who subsequently developed a first episode of psychosis. The white matter abnormalities were seen particularly in the superior longitudinal fasciculus (SLF) and were associated with increased severity of symptomatology. The overall degree of white matter alteration was also significantly related to clinical outcome 15 months later.
Editor’s Note: The SLF is a major neuronal conduit between prefrontal cortical systems, which are responsible for cognition and planning, and the parietal cortex, which is responsible for spatial abilities. Disruption of this fiber track has been related to difficulties in social cognition and “theory of mind” concepts, like inferring what others might be thinking.
At a recent conference Robin Murray, a researcher based in London, gave a talk about the potential adverse effects of tetrahydrocanabinol (THC). Considerable data indicate that chronic long-term smoking of marijuana is associated with the doubling of the risk of psychosis. Moreover, if a marijuana user has a common genetic variant in the catechol-o-methyltransferase enzyme (COMT), they are at substantially increased risk for the development of psychosis. New data also indicate that frequent use of marijuana can also be associated with an earlier onset of schizophrenic psychosis than would ordinarily occur without the substance use. Data also suggest that the psychosis associated with THC use is more difficult to treat than that without such use.
Murray also reported on a new risk that is associated with more potent new products. Older, natural forms of marijuana contained a compound called cannabidiol, which is associated with calming effects and possible antipsychotic effects. In a new synthetic preparation of THC called skank or spice, there is a higher amount of THC, but none of the positive diol compound. Thus there are some important caveats to the prevailing view that marijuana is relatively harmless.
Editor’s Note: Marijuana use brings a clear-cut increased risk for psychosis, which appears to interact with a common gene polymorphism and which is increased with use of a new synthetic preparation called skank or spice. If a marijuana user has a concurrent mood disorder, the risks appear to be even greater. The one sure pharmacological effect of marijuana is an amotivational syndrome, and motivational deficits are one of the core components of depression.
Given the difficulty of treating the mood and schizophrenic disorders, a patient should not risk worsening their illness with marijuana. N-acetylcysteine is one treatment option that may bring about decreased craving for and avoidance of marijuana and a number of other abused substances, as well as being helpful for mood and negative symptoms in schizophrenia.
Omega-3 fatty acids are important for brain development and function and are essential to the human diet since they cannot be synthesized by the body. Omega-3 fatty acids are derived from canola oil, walnuts, flax seed oil, leafy vegetables, and especially fish. The main omega-3 fatty acids include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They have anti-inflammatory effects, unlike omega-6 fatty acids, which are pro-inflammatory. The omega-6 fatty acids come from soy, peanuts, corn oil, and meats, and are associated with increases in obesity, myocardial infarction, and stroke.
In a recent review of the literature, John Davis and Joe Hiblen found that diets that include high levels of omega-3 fatty acids are associated with decreased incidence of depression, suicide, and cardiovascular disease. The researchers performed a meta-analysis of all the prospective depression treatment studies of omega-3 fatty acids compared to placebo. They found that EPA had antidepressant effects in humans, with moderate effect size and a high degree of statistical significance. DHA, however, did not appear to have an antidepressant effect, and pure DHA was even associated with some worsening of depression.
Editor’s note: This meta-analysis helps clarify some of the ambiguities in the literature about the antidepressant efficacy of the omega-3 fatty acids, clarifying that EPA alone is an effective antidepressant. The one study that did not find antidepressant effects with EPA was carried out by the Bipolar Collaborative Network, in which I am an investigator. Our study, published in an article by Keck et al., showed that 6g of EPA was not significantly more effective than placebo in bipolar depression or in rapid cyclers. However, there is some indication that 6g may be too high a dose of EPA, and most of the recommendations now suggest using 1-2g of either EPA or an EPA/DHA combination. Read more
There are no FDA-approved treatments for children under age 10 with bipolar disorder. For an article in Psychiatric Annals, this editor and Janet Wozniak asked experts how they would sequence treatment of a hypothetical case of a 6-year-old with extreme mood instability consistent with a diagnosis of BP -NOS (see Table I). We also asked how the experts would treat a different case of a 9-year-old with a full-blown psychotic BP-I mania (see Table II).
The results are presented and discussed in detail in the article, and are presented here to reinforce several points. The recommendations for children under 10 and for BP NOS are highly similar to consensus guidelines for older BP I children compiled by Kowatch et al.
Treatments in the face of non-response to option A or others are sequenced differently by different experts, but almost always involve an atypical antipsychotic (AA) or a mood stabilizer (MS) such as lithium, valproate, carbamazepine/oxcarbazepine, or rarely, lamotrigine. Revisions of atypical antipsychotics and mood stabilizers and use of combinations are the common next strategies.