Psychiatric Medications Just as Effective as Medications for Other Illnesses
The popular media has sometimes scrutinized research on psychiatric medications, suggesting that they are not as effective as pharmaceutical companies would have us believe. Researchers in Germany recently performed a meta-analysis of research on psychiatric medications and found that the effect sizes for psychiatric drugs were comparable to effect sizes of other types of drugs. (Effect sizes communicate the size of the change that a drug brings about in patients.) The study was published in the British Journal of Psychiatry.
From the abstract:
Any comparison of different outcomes in different diseases can only serve the purpose of a qualitative perspective. The increment of improvement by drug over placebo must be viewed in the context of the disease’s seriousness, suffering induced, natural course, duration, outcomes, adverse events and societal values.
Antidepressants Work Better in Major Depressive Disorder than Previously Thought
As we’ve written before, the popular media has sometimes questioned the efficacy of antidepressants for unipolar depression. A reanalysis of data from previous controlled trials of fluoxetine and venlafaxine that was recently published in the Archives of General Psychiatry provides new evidence that these drugs are significantly more efficacious than placebo in youth, adult, and geriatric populations with major depressive disorder.
The researchers concluded,
To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.
Study Calls Into Question FDA Black Box Warning about Suicide Risk in Youth Taking Antidepressants
In 2004, the Federal Drug Administration issued a “black box warning” about increased risk of suicidal thoughts and behavior in children and adolescents taking selective serotonin reuptake inhibitors (SSRIs). See here for an overview from the National Institute of Mental Health.
An article published in the Archives of General Psychiatry earlier this year analyzed data from studies of fluoxetine and venlafaxine in youth, adults, and geriatric patients to determine if antidepressant use is linked to suicide. The drugs decreased both depressive symptoms and suicidal thoughts and behavior in adults and the geriatric population. They seemed to have no effect on suicidal thoughts or behavior in the youth.
For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication.
Weight Gain and Metabolic Risks of Antipsychotic Drugs in Children and Adolescents
A study published in the Journal of Child and Adolescent Psychopharmacology in late 2011 reviewed the various weight and metabolic side effects of drugs like olanzapine, clozapine, risperidone, quetiapine, and aripiprazole.
Across 34 published head-to-head and placebo-controlled studies in youth with psychotic and bipolar disorders, weight gain ranged from 3.8 to 16.2 kg with olanzapine (n=353), 0.9-9.5 kg with clozapine (n=97), 1.9-7.2 kg with risperidone (n=571), 2.3-6.1 kg with quetiapine (n=133), and 0-4.4 kg with aripiprazole (n=451).
Exercise and Brain Health: Some Good Points to Remember
In a review article in the Neuroscientist published in February of this year, Kirk I. Erickson and collaborators wrote that “[m]ajor depressive disorder is considered a risk factor for Alzheimer’s dementia and memory impairment and is associated with less BDNF and greater hippocampal atrophy, possibly through a BDNF pathway. However, exercise and effective treatment for geriatric depression increases BDNF levels, increases serotonin fibers, is associated with greater hippocampal volumes, and reduces the risk for Alzheimer’s dementia.”
Editor’s note: Not a bad set of benefits from exercise! The researchers suggest that exercise is extremely important in reversing the decreases in brain-derived neurotrophic factor (BDNF) associated with depression, helping to improve depressed mood, increasing cardiovascular fitness, and maintaining healthy cognition.
Hippocampal volume and BDNF levels in blood both decrease with age. Yet exercise increases both BDNF and the formation of new neurons (neurogenesis) in animals. New data in humans suggest that aerobic fitness is associated with the size of the hippocampus, both in both children and adults. It is not clear yet whether this increase in hippocampal volume is directly driven by increases in BDNF and/or neurogenesis. However, since a smaller hippocampus is a risk factor both for depression and for mild cognitive impairment progressing to Alzheimer’s dementia, attempting to enhance hippocampal volume in any way possible is probably a good idea.
Methods of increasing hippocampal volume include treatment with antidepressants or with lithium. In the 2012 paper Erickson and collaborators also wrote, “Anaerobic exercise enhances executive and memory function and reduces hippocampal atrophy in late adulthood, and this may be partially mediated through a BDNF pathway.”
Erickson and collaborators conducted a longitudinal study published in 2010 that quantified the amount of physical activity subjects engaged in by calculating the total number of blocks walked per week. Individuals reporting greater amounts of physical activity at the beginning of the study had, upon examination nine years later, greater gray matter volume in several parts of the brain, including the hippocampus. This effect was “dose-dependent,” meaning that only those individuals who walked at least 72 blocks per week (roughly equivalent to 1 mile per day) had significant sparing of brain tissue nine years later. The study found increased gray matter volume in the prefrontal cortex and in the temporal lobe.
After a further follow-up of four more years, greater gray matter volume with physical activity was associated with a two-fold reduced risk of cognitive impairment. The researchers concluded that “physical activity patterns earlier in life were linked to brain volume and cognitive impairment later in life.”
There are a number of important points to remember about cognitive impairment. One is that increasing hippocampal volume and preventing its decrement with aging may help prevent age-related memory loss and potentially the rapidity at which mild cognitive impairment progresses. Read more
Mothers’ SSRI Use May Lead to Increased Risk of Pulmonary Hypertension in Infants
The New York Times summarized findings about the effect of mothers’ antidepressant use on enfants from an article published by Kieler et al. in the British Medical Journal this year.
Researchers have long suspected a link between the use of selective serotonin reuptake inhibitors, or S.S.R.I.’s, and [pulmonary hypertension in babies], but previous studies have been small and inconclusive (with results ranging from there being no link to a six times greater risk).
This research, based on 1.6 million births in Denmark, Finland, Iceland, Norway or Sweden from 1996 to 2007, showed that among women using S.S.R.I.’s, the risk of persistent pulmonary hypertension for infants more than doubled (particularly for use late in pregnancy). It’s still a small risk: 3 in 1000 births, as opposed to 1.2 per 1000 births overall. But it’s a small risk of a serious problem.
Pulmonary hypertension, Dr. Juliette Madan, a pediatrician at the Dartmouth Hitchcock Medical Center explained, is diagnosed when an infant struggles to get enough oxygen into her lungs, and therefore into her bloodstream. The condition can be deadly, although Dr. Madan said that it’s usually treatable — with possible lifelong consequences.
But other research suggests that untreated depression during pregnancy has its own risks, including pre-term birth and low birth weight. Given that, how should a pregnant woman and her doctor weigh the competing risks?
See the New York Times for a discussion on how to balance mother’s health with babies’ health.
Quetiapine May Be an Effective Monotherapy for Bipolar I
An article published by Weisler et al. last year in the Journal of Clinical Psychiatry suggests that quetiapine may be effective as a monotherapy maintenance treatment for bipolar I disorder. It has previously been shown to work in combination with lithium or divalproex and is approved by the Federal Drug Administration for this combination treatment.
Adult patients diagnosed with bipolar I disorder who were currently or recently in a mood episode received open-label quetiapine in doses of 300-800mg per day for up to 24 weeks. Patients who became stable either remained on quetiapine or were switched to lithium (at doses of 0.6-1.2 mEq/L) or placebo. This double-blind phase of the study continued for up to 104 weeks.
The study began with 2,438 patients, 1,172 of whom made it to the second phase of the trial. On the main outcome measure of time to recurrence of any mood event, both quetiapine and lithium were significantly better than placebo.
Editor’s Note: In the 50% of patients with a recent mood episode who were able to be stabilized on quetiapine monotherapy, those who remained on long-term quetiapine or those who switched to lithium were both much less likely to have subsequent relapses into either depression or mania than those who switched to placebo. Whether Astra-Zeneca, the company that produces quetiapine, will file to gain Federal Drug Administration approval of quetiapine monotherapy for long-term preventive treatment is not known.
Creative People More Likely to Have Mental Illness
Mozart
According to a large family study of people with severe mental disorders that was published by Kyaga et al. in the British Journal of Psychiatry last year, people with bipolar disorder and siblings of people with schizophrenia or bipolar disorder were much more likely to be working in creative professions than people without severe mental illness.
Kyaga talked to Medscape Medical News about the study:
“I think the study stresses the importance of treating all patients individually, and with the aim of finding the optimal treatment with regards to effectiveness, while minimizing the adverse effects that medication can have on positive aspects of psychiatric disorders,” Dr. Kyaga said.
“We often encounter the suggestion that lithium reduces creativity in patients with bipolar disorder and that adherence therefore is difficult. Now we can say that it is true that bipolar disorder is in fact associated with increased creativity, but we also know from previous research that terminating treatment with lithium in bipolar disorder will, in the long run, disrupt creative behavior,” he continued.
“We therefore need to pay close attention to what patients tell us while being treated, so that we can find a regimen that will work for them to prevent the disastrous consequences of severe psychiatric disorder, while providing them opportunities to uphold their creative behaviors in the long run,” Dr. Kyaga said.
Prenatal BPA Exposure Might Lead to More Hyperactivity, Depression, and Anxiety in Young Children
BPA can be found in the lining of cans.
An article published by Braun et al. in Pediatrics last year suggests that children who were exposed to higher levels of BPA while in the womb exhibited more anxious and depressed behaviors and poorer emotional control and inhibition at age 3. Braun described the implications of this finding to Medscape Medical News:
“At this point, we don’t know what these findings mean in terms of clinical disorders of behavior,” Joe M. Braun, MSPH, PhD, from the Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, told Medscape Medical News. “Future studies will need to determine if BPA exposures are associated with clinical behavior disorders,” he said.
BPA is used in a variety of consumer products, including dental sealants, food/beverage containers and linings, medical equipment, and thermal receipts, such as those from ATM machines. Virtually all people in industrialized nations are exposed to the plasticizer.
“People who are concerned about BPA exposure could decrease or eliminate their consumption of canned or packaged foods; they could also avoid contact with thermal receipts,” Dr. Braun said.
Omega-3 Fatty Acids Could Help Treat ADHD in Children
An article by Bloch & Qawasmi published in the Journal of the American Academy of Child and Adolescent Psychiatry last year suggested that omega-3 fatty acids could improve ADHD in children. The effects were milder than the standard pharmacological treatments for ADHD, but given that omega-3s have few side effects, there would be little risk to using them to supplement traditional treatments or in cases where traditional treatments cannot be used.
Editors note: It would also be worth seeing if omega-3s helped mood symptoms too. A meta-analysis we wrote about here suggests that the omega-3 fatty acid EPA or the combination of EPA plus DHA has positive effects on depression in adults.
