A new study has found that children and adolescents taking a high
dose of antipsychotics are almost twice as likely to die of any cause
than children on other types of medications. Perhaps even more striking,
children taking high doses of antipsychotics were more than four times
as likely to die of cardiovascular or metabolic causes than children on
other medications.
The study, published online in JAMA Psychiatry, was led by
Wayne A. Ray, PhD, at the Vanderbilt University School of Medicine. The
data was captured between 1999 and 2014. The researchers included youths
between the ages of 5 and 24 years old, who were recipients of Medicaid
insurance in Tennessee. This allowed the researchers to examine their
medical records. In total, there were about 250,000 individuals in the
study. The researchers excluded children with severe physical illness
diagnoses, tic disorders, and schizophrenia. The most common included
diagnosis was ADHD. Photo Credit: Public DomainThe study was composed of three groups: a control group who were on
medications such as stimulants or antidepressants; a group who were
prescribed a low dose of an antipsychotic, and a group prescribed a high
dose of an antipsychotic.
The group taking a low dose of antipsychotics did not have a
significantly increased risk of death when compared to the group taking
other medications. However, children taking a high dose of
antipsychotics were 1.8 times more likely to die of any cause, 3.5 times
more likely to die of unexpected causes (not including overdose), and
4.29 times more likely to die of cardiovascular or metabolic problems.
Deaths from suicide were no different between groups.
In total, there were 40 deaths out of the 27,354 in the higher-dose
group (0.15%), compared to 67 deaths out of the 123,005 in the control
group (0.05%).
Of course, there could be other confounding factors that led to this
effect—something present in the higher-dose group that was not present
in the control group. However, the researchers controlled for the most
obvious explanations (diagnosis, medical illness, and any medication
use). Additionally, after the researchers ran a sensitivity analysis,
they concluded that “to explain the risk of unexpected death in the
higher-dose group, the confounder would have to increase risk by 5-fold,
have a 75% prevalence in the higher-dose antipsychotic treatment group,
and not be present in control patients.”
The potentially deadly cardiovascular and metabolic adverse effects
of antipsychotic medications are well-documented, but according to the
researchers, this is one of the first large studies to examine whether
children are at a greater risk of death due to these causes. The
researchers write that after the second generation of antipsychotic
medications was invented, these drugs began to be prescribed in younger
patients for all variety of indications, such as ADHD, depression, and
behavioral control—indications for which other, safer therapies might be
a better option. According to the authors,
“The study findings appear to reinforce existing
guidelines for improving the outcomes of antipsychotic therapy in
children and youths. These guidelines include restriction to indications
for which there is good evidence of efficacy, an adequate trial of
alternatives including psychosocial interventions when possible,
cardiometabolic assessment before treatment and monitoring after
treatment, and limiting therapy to the lowest dose and shortest duration
possible.”
****
Ray, W. A., Stein, M., Murray, K. T., Fuchs, C., Patrick, S. W.,
Daugherty, J. . . . Cooper, W. O. (2018). Association of antipsychotic
treatment with risk of unexpected death among children and youths. JAMA Psychiatry. Published online ahead of print Dec. 12, 2018. doi:10.1001/jamapsychiatry.2018.3421 (Link)
MIA-UMB News Team: Peter
Simons comes from a background in the humanities where he studied
English, philosophy, and art. Now working on his PhD in Counseling
Psychology, his recent research has focused on conflicts of interest in
the psychopharmaceutical research literature, the use of antipsychotic
medications in the treatment of depression, and the general
philosophical and sociopolitical implications of psychiatric taxonomy in
diagnosis and treatment.
According to new research, between 2013 and 2014, 38.4% of adults took a medication that lists depression as a potential side effect, and 9.5% received three or more such medications. About 23.5% took a drug that listed increased suicidality as a side effect. The researchers found that the use of these drugs was associated with people developing depression and suicidality.
“Use of prescription medications that have depression as a potential adverse effect was common and associated with greater likelihood of concurrent depression,” the researchers write.
The research, published in the Journal of the American Medical Association (JAMA), was led by Dima M. Qato, PharmD, MPH, PhD, at the Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, and also included Katherine Ozenberger, from that same institution, as well as Mark Olfson, a psychiatrist and public health specialist from Columbia University, New York.
Numerous medications include depression and suicidality as a potential side effect, including hormonal contraceptives, beta-blockers, proton pump inhibitors, anti-anxiety medications, and, paradoxically, “antidepressants” themselves.
The researchers found that rates of depression were higher in those taking medications that listed depression as a side effect. They controlled for numerous other factors, including gender, race, age, education level, socioeconomic status, marital status, employment, and multiple medical conditions (e.g., hypertension, cancer, diabetes, and many others).
The authors also controlled for potential confounds and reverse causality by using a statistical method called sensitivity analyses. For instance, the researchers conducted additional analyses to test if removing those who used psychotropic medications would alter the outcome, or if removing those who had hypertension (which is also associated with depression) would alter the outcome. In all of these cases, the association between medication use and depression continued to be statistically significant.
These results indicate that even when removing potential confounding cases (such as other psychotropic drugs, or people with illnesses linked to depression), there was still a link between medication use and the development of depression.
The connection between these drugs and depression were even more powerful for people who took three or more medications that had depression as a side effect. In fact, according to the researchers, about three times as many people who took three or more of these drugs developed depression when compared to those who were not on such medications:
“The estimated prevalence of depression was 15% for those reporting use of 3 or more medications with depression as an adverse effect vs 4.7% for those not using such medications.”
Their finding was not merely due to medication use in general—there was no difference in depression symptoms between those who took no medication and those who took even three medicines that did not have depression as a side effect. Thus, only drugs with depression listed as a side effect were associated with the development of depression.
According to the researchers, some of these medications are available over-the-counter (such as proton pump inhibitors and emergency contraceptives) in the US, and their packaging is often not thorough enough to describe the association of these drugs with depression and suicidality. Thus, consumers may not be aware that the medications they are taking could be responsible for their altered emotional state.
Additionally, the researchers note that calls for screening for depression have expanded considerably—yet screening instruments do not ask about potential medication side effects. Thus, screening for depression may result in someone receiving a diagnosis of depression (and potentially receiving antidepressants) when what is happening is that they are experiencing the side effect of another medication.
****
Qato, D. M., Ozenberger, K., Olfson, M. (2018). Prevalence of prescription medications with depression as a potential adverse effect among adults in the United States. JAMA, 319(22), 2289-2298. doi:10.1001/jama.2018.6741 (Link)
In the first systematic review of withdrawal problems that
patients experience when trying to get off SSRI antidepressant medications, a
team of American and Italian researchers found that withdrawing from SSRIs was
in many ways comparable to trying to quit addictive benzodiazepine sedatives
and barbiturates. Publishing in Psychotherapy and Psychosomatics, they also
found that withdrawal symptoms can last months or even years, and entirely new,
persistent psychiatric disorders can emerge from discontinuing SSRIs. The authors analyzed 15 randomized controlled studies, 4 open
trials, 4 retrospective investigations and 38 case reports of SSRI withdrawal. They found
that paroxetine (Paxil) was the worst, but that all the SSRI
antdepressants could cause a wide range of withdrawal symptoms from dizziness,
electrical shock sensations and diarrhea to anxiety, panic, agitation, insomnia
and severe depression.
The prevalence of such withdrawal syndromes was
"variable" and difficult to estimate from the studies, they wrote,
but generally seemed very common. "Symptoms typically occur within a few
days from drug discontinuation and last a few weeks, also with gradual
tapering. However, many variations are possible, including late onset and/or
longer persistence of disturbances. Symptoms may be easily misidentified as
signs of impending relapse."
"Clinicians need to add SSRI to the list of drugs
potentially inducing withdrawal symptoms upon discontinuation, together with
benzodiazepines, barbiturates, and other psychotropic drugs," they
concluded. "The term ‘discontinuation syndrome' that is currently used
minimizes the potential vulnerabilities induced by SSRI and should be replaced
by ‘withdrawal syndrome'."
An accompanying editorial noted that, "This type of
withdrawal consists of: (1) the return of the original illness at a greater
intensity and/or with additional features of the illness, and/or (2) symptoms
related to emerging new disorders. They persist at least 6 weeks after drug
withdrawal and are sufficiently severe and disabling to have patients return to
their previous drug treatment. When the previous drug treatment is not
restarted, post-withdrawal disorders may last for several months to
years."
The editorial also stated that, "With SSRI withdrawal,
persistent postwithdrawal disorders may appear as new psychiatric disorders, in
particular disorders that can be treated successfully with SSRIs and SNRIs.
Significant postwithdrawal illnesses found with SSRI use include anxiety
disorders, tardive insomnia, major depression, and bipolar illness."
While the study authors found no difference between gradual
tapering over relatively short periods and abrupt discontinuation of SSRIs, the
editorial authors argued that there was evidence to suggest benefits to
tapering.
Chouinard G, Chouinard V, -A, New Classification of Selective
Serotonin Reuptake Inhibitor Withdrawal. Psychother Psychosom 2015;84:63-71.
DOI:10.1159/000371865 (Abstract and
full text)
Fava, G.A., A. Gatti, C. Belaise, J. Guidi, and E. Offidani.
“Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor
Discontinuation: A Systematic Review.” Psychotherapy and Psychosomatics 84, no.
2 (2015): 72–81. (Abstract and
full text)
Common psychiatric medications double the risk of heart attack and triple the risk of stroke, according to research presented at the Canadian Cardiovascular Congress and reported in theVancouver Sun. Another study reported that mental health patients often receive poor medical care and general health recommendations from their treatment providers, contributing further to their heart problems.
“While evidence linking some antipsychotic medications to weight gain, diabetes and heart disease has grown in recent decades, this is the first time it has been documented nationally,” reported theSun about the research led by a PhD student working with University of British Columbia and the Toronto Centre for Addiction and Mental Health, using data from the Canadian Community Health Survey by Statistics Canada.
Many psychiatric medications “change the way fats and sugars are broken down in the body leading to high cholesterol or diabetes, which are both contributing causes to heart disease and stroke,” reported the Sun.
High rates of smoking among people taking psychiatric medications, unhealthy eating and physical inactivity exacerbate the problems. Another recent study in Vancouver, the Sun reported, “concluded patients with schizophrenia who develop heart disease rarely receive adequate followup treatment.”
“Fifteen years ago, this wasn’t even considered part of treatment. Now care has to include discussion of metabolic syndrome,” a co-author of that study told the Sun. “All patients should be on an exercise program because that has been shown to have positive impact … Exercise can help reverse the (side) effects of the medication.”
“Evidence from longitudinal, cross-sectional, and prospective cohort studies suggests that the use of antidepressants at therapeutic doses is associated with decreased bone mineral density and increased fracture risk,” reported researchers in a mini-review of the scientific literature published in Endocrine.
The Belgian University of Liège researchers expressed concern that SSRIs are often prescribed to older adults at high risk for bone fractures. The level of risk differs “depending on dose, exposure duration, time of exposure, age, or sex,” they wrote. “However, the risk of fracture declined rapidly after discontinuation of use of SSRIs. The evidence now seems sufficient to consider adding SSRIs to the list of medications that contribute to osteoporosis.”
People diagnosed with schizophrenia experience reductions in brain volume that increase over time, and the amount of those reductions increases in proportion to the quantities of antipsychotics taken and not symptom severity, according to research reported in PLOS One. Investigators from the University of Oulu in Finland performed brain scans on 33 participants diagnosed with schizophrenia and 71 control participants over a ten-year period, and found reductions in the antipsychotic users especially pronounced in the temporal lobe and periventricular area.
Even after adjusting for alcohol use and weight gain, the researchers found that “mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls.”
“Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia,” stated the researchers. “The amount of antipsychotic medication… over the follow-up period predicted brain volume loss.”
