No Association of Benzodiazepines, Z Drugs and Other Anxiolytics with Dementia
Benzodiazepines, so-called Z-drugs (such as zolpidem, zopiclone, and zaleplon), and other anxiolytics are commonly prescribed drugs that have some cognitive side effects. For this reason, there has been concern that the drugs may increase risk of dementia, and small studies had suggested that this might be the case. However, a new large study found no subsequent dementia risk after taking these drugs.
In a 2020 article in the American Journal of Psychiatry, researchers Merete Osler and Martin Balslev Jørgensen described a cohort and nested case-control study of 235,465 adult patients in Denmark in which they found no association of benzodiazepines, Z-drugs, or other anxiolytics with a subsequent diagnosis of dementia. Participants were patients over the age of 20 who were hospitalized for an affective disorder. Of these, 75.9% had been prescribed one of the drugs in question, and 4.2% went on to be diagnosed with dementia.
While participants in this study who had the lowest use of benzodiazepines or Z drugs showed a minimal increased risk of dementia compared to those who took none of these drugs, those who had the highest use of benzodiazepines and Z drugs actually had the lowest incidence of dementia in the study.
The previous studies may have been “confounded by indication” meaning they did not take the underlying psychiatric condition for which the drugs were prescribed into account.
Characteristics of Youth with Bipolar Spectrum Disorders
In a 2020 article in the Journal of Child and Adolescent Psychopharmacology, researcher Gonzalo Salazar de Pablo and colleagues described characteristics of youth with three different bipolar spectrum disorders: bipolar I disorder, bipolar disorder not otherwise specified (NOS) and mood disorder (MD) not otherwise specified. The participants were hospitalized adolescents aged 12–18 years, who were highly impaired with hallucinations, delusions, incoherence, or inability to function.
Mania (especially irritability) and depressive symptoms were common in all three groups.
Many of the youths had comorbid conditions. Approximately 40% of each diagnosis group had an anxiety disorder. Attention deficit hyperactivity disorder (ADHD) was seen in 29.2% of those with bipolar I disorder, 34.5% of those with bipolar NOS, and 43.5% of those with mood disorder NOS. Oppositional defiant disorder was seen in just over 20% of those with bipolar I or bipolar NOS, and just over 30% of those with mood disorder NOS. Substance use disorders were seen in 8.3% of those with bipolar I and about 21% of those with bipolar NOS or mood disorder NOS. Many of the participants had moderate to severe suicidality.
The median delay before the adolescents received treatment for their moderate to severe symptoms was 21 to 25 weeks. After discharge from the hospital, the adolescents with bipolar I, bipolar NOS, and mood disorder NOS were typically treated with atypical antipsychotics (79.2%, 62.1%, and 56.5%, respectively), mood stabilizers (66.7%, 31.0%, and 34.8%), and lithium (58.3%, 20.7%, 30.4%), with greater use of mood stabilizers and lithium than on admission and less use of antidepressants. Few children were on ADHD medications on admission, and even fewer (4-9%) on discharge.
The authors conclude: “Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a [long] period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing [bipolar disorder] or other affective episodes requiring hospitalization.”
Editor’s Note: These findings replicate many others in the field indicating that children with bipolar spectrum disorders, even those with symptoms short of a full-blown bipolar I diagnosis, are highly impaired with multiple comorbidities and high levels of suicidality and other dangerous symptoms. These patients deserve systematic pharmacological intervention based on an extensive clinical treatment literature.
The only thing the authors failed to address is that not only does no such clinical treatment literature exist, but there does not seem to be any recognition by the National Institute of Mental Health and other funding bodies that a series of treatment-oriented studies in children and adolescents is urgently needed.
The 2010 epidemiological studies of Kathleen Merikangas and colleagues indicate that 2.2% of adolescents have a bipolar spectrum diagnosis and that 80% of those young people are not in any kind of treatment. This is in part driven by a lack of consensus about appropriate treatment. The magnitude and seriousness of this illness creating lifelong problems, disability, cognitive impairment, and the loss of more than a decade of life expectancy is a public health catastrophe.
In the 1980s, AIDS protesters had to raise awareness, protest, and clamor for treatment studies in a highly confrontational manner before AIDS research was appropriate funded. Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease since 1984, has said he was finally convinced that the AIDS protestors were correct, and he then joined forces with them to foster and accelerate treatment studies. The prognosis for AIDS changed from certain death in the 1980s to a manageable illness today.
We need leaders to demand attention to the lack of studies in bipolar disorder at a threshold that cannot be ignored by leaders of the NIMH. Patient advocacy groups must push the NIMH to fund treatment studies for bipolar disorder. It is clear that without some new form of pressure, the NIMH will fail in its stated mission to help make the lives of those with serious mental illness less grave. The current generation and many in the future generations of patients with bipolar disorder will otherwise face disaster.
