No Association of Benzodiazepines, Z Drugs and Other Anxiolytics with Dementia

October 13, 2020 · Posted in Current Treatments, Risk Factors · Comment 

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

October 5, 2020 · Posted in Diagnosis, Risk Factors · Comment 

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.

Early Precursors of Mood Disorders in Young Children of Parents with Bipolar or Unipolar Disorder

July 24, 2020 · Posted in Course of Illness, Risk Factors · Comment 

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Caroline Vandeleur presented findings from a 13-year study of children in Switzerland who have a parent with bipolar disorder or major depressive disorder. In contrast to findings from the US presented by Danella Hafeman, Vandeleur and colleagues found no evidence of psychopathology in 4 year-olds. They did find that in 7-year-olds, children of a parent with major depressive disorder were four times more likely to have a separation anxiety disorder. In an overall sample of 449 children with a mean age of 10 who were followed up for 13 years, major depression tended to be preceded by anxiety disorders. Participants who went on to be diagnosed with bipolar disorder had earlier symptoms of depression, subthreshold hypomania, conduct disorders, and drug abuse. These were especially common in those who had a parent with bipolar disorder.

Editor’s Note: These data indirectly confirm other observations in which children at high risk for mood disorders in the US showed earlier signs of psychopathology than those in other countries including the Netherlands and Canada.

Clinical Risk Prediction in Youth at Risk for Bipolar Spectrum Disorder and Relapse

July 21, 2020 · Posted in Course of Illness, Diagnosis, Risk Factors · Comment 

Researchers from two 15-year studies of bipolar youth, COBY (The Coarse and Outcome of Bipolar Youth Study) and BIOS (Bipolar Offspring Family Study), have used the longitudinal data from their studies in order to create a risk calculator that can predict an individual’s likelihood of illness.

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Danella Hafeman presented research on a risk calculator that predicts the 5-year risk for onset of a bipolar disorder spectrum diagnosis (BPSD) in young people at high risk and can reasonably distinguish those who will receive a diagnosis from those who will not.

Some of the factors used in the risk calculator include dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and the age at which parents were diagnosed with a mood disorder.

Hafeman reported that there was a 25% risk that offspring of a bipolar parent would develop a bipolar disorder spectrum diagnosis. In a population ranging in age from 6 to 18 years, Hafeman and colleagues found that anxiety and depression symptoms were a sign of vulnerability to a bipolar spectrum disorder, while subthreshold manic symptoms indicated that a bipolar spectrum disorder could soon emerge. Sudden or exaggerated changes in mood were also an important predictor of BPSD.

Hafeman and colleauges noted that even in children as young as 2 to 5 years old, there were already signs of anxiety, aggression, attention problems, depression, and sudden mood changes in those who would go on to receive a diagnosis of bipolar spectrum disorder.

The researchers were also able to predict which patients with BPSD would have a relapse. According to Hafeman and colleagues, “The most influential recurrence risk factors were shorter recovery lengths, younger age at assessment, earlier mood onset, and more severe prior depression.”

Editor’s Note: Offspring of a parent with bipolar disorder are at high risk for anxiety, depression, attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and bipolar disorder. Parents should be alert for the symptoms of these illnesses and seek evaluation and treatment for their children as necessary. Parents should also be aware of the risk factors above that contributed to the risk calculator.

Parents can aid physicians in their evaluation by joining our Child Network and keeping weekly ratings of their children’s symptoms of depression, anxiety, ADHD, oppositional behavior, and mania.

Increased Risk for Dementia in Bipolar Disorder

July 14, 2020 · Posted in Comorbidities, Risk Factors · Comment 

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Flavio Kapczinski described a recent meta-analysis of 10 studies that found that bipolar disorder is a risk factor for dementia, and that lithium treatment can decrease the incidence of dementia in people with bipolar disorder.

The ten studies included a total of 6,859 participants with bipolar disorder and 487,966 healthy control participants. People with bipolar disorder were 2.96 times more likely to develop dementia than those without bipolar disorder. Five of the studies included information about  treatment with lithium, which was found to decrease the risk of dementia among those with bipolar disorder by a little more than half (0.54).

Five studies also revealed that the risk of progression to dementia was higher among those with bipolar disorder than among those with major depressive disorder. In addition, one of the ten studies explored predictors of dementia in people with bipolar disorder and found that those who experienced more mood episodes had a higher risk of dementia.

Editor’s Note: It appears that the number of mood episodes a person experiences predicts dementia, and it has previously been found to predict the emergence of cognitive impairment. Prevention is the name of the game, and lithium is the best defense. My new mantra: “Prevent Episodes, Protect the Brain, Use More Lithium.”

Bipolar Disorder in Pregnancy and the Postpartum Period

July 3, 2020 · Posted in Risk Factors · Comment 

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Veerle Bergink reported several findings from a recent meta-analysis of articles on pregnancy and bipolar disorder. Bergink and colleagues found that pregnant women with bipolar disorder have a 37% risk of a postpartum relapse, more than twice the risk of postpartum mental disorders in the general population.

Using lithium as a treatment in the first trimester of pregnancy increased risk of congenital malformations in the fetus, but the risk was much smaller than previously thought and could be monitored by ultrasound.

Bergink and colleagues also reported that in a sample of 645 women with first-onset postpartum psychosis who received followup over a period of 7 to 25 years, 43% had no subsequent severe episodes outside of the postpartum period.

Another finding was that women with postpartum severe depression or mania had abnormalities in T cells, which are important in immune response.

Childbirth and Bipolar Disorder

June 30, 2020 · Posted in Risk Factors · Comment 

In an abstract for virtual presentation at the 2020 meeting of the International Society for Bipolar Disorders, researcher Ian Jones presented evidence that childbirth may trigger onset of bipolar disorder.

Jones found that 15% of women who experience postpartum mood disorders shortly after childbirth will go on to develop bipolar disorder over time. A previous diagnosis of bipolar affective disorder is the biggest predictor that a woman will be readmitted for treatment of postpartum mental illness.

In addition, one of the biggest risk factors for postpartum mental disorders is a family history of bipolar disorder in first-degree relatives. The risk of postpartum mental disorders also increases when first-degree relatives have a psychiatric illness of any kind.

Editor’s Note:  These data are consistent with research on sensitization/kindling, the idea that while early mood episodes may be triggered by psychosocial stress and other endocrine factors, later episodes may emerge more spontaneously.  In this case, the stress associated with childbirth can lead to a subsequent bipolar diagnosis (with or without a precipitating stressor) in the future.

The psychosocial stress of childbirth and subsequent sleep deprivation can be severe, and those with a history of a mood disorder should seek additional support during such a time.

Cannabis Use in Adolescence Linked to Depression and Suicidality in Young Adulthood

April 24, 2020 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 
Photo by Louis Hansel @shotsoflouis on Unsplash

In a meta-analysis published in the journal JAMA Psychiatry in 2019, researcher Gabriella Gobbi and colleagues analyzed findings from 11 studies including a total of 23,317 participants and found that cannabis use in adolescence (before age 18) was associated with a significantly increased risk of depression, suicidality, and suicide attempts in young adulthood (between 18 and 32 years of age).

The researchers did not find a link between cannabis use and anxiety.

Editor’s Note: Cannabis use is not as harmless as many teens may believe.

In Animal Model, Long-Term THC Exposure Interferes with Cortical Control of the Nucleus Accumbens

April 21, 2020 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 
Cannabis plant. Photo by Esteban Lopez on Unsplash

In an article in the journal Biological Psychiatry, researchers Eun-Kyung Hwang and Carl R. Lupica reported that in rats, long-term use of THC (tetrahydrocannabinol) weakens input from the cortex to the reward area of the brain, the nucleus accumbens (NAc). Long-term THC use also strengthens connections to the NAc from emotional control (limbic) regions, such as the basolateral amygdala and ventral hippocampus. Hwang and Lupica reason that this shift from cortical control of the NAc to limbic control likely contributes to the cognitive and psychiatric symptoms associated with cannabis use.

Editor’s Note: Street marijuana largely contains THC rather than CBD, the beneficial, anxiety-reducing component of cannabis. Cannabis products are being decriminalized, but it is important to remember that those with THC are linked to cannabis use disorder and increased susceptibility to psychiatric illness. Patients with bipolar disorder who use marijuana also have a more adverse course of illness than those who do not use it.

One Hit of THC Tied to Psychotic Symptoms in Adults with No History of Mental Illness

April 17, 2020 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 
A woman rolls a joint. Photo by Thought Catalog on Unsplash

In a meta-analysis published in the journal Lancet Psychiatry, researcher Guy Hindley and colleagues reported that in otherwise healthy adults, a single dose of THC (equivalent to smoking one joint) produced transient psychotic symptoms.

The meta-analysis included 9 studies with a total of 196 participants. The researchers included studies in which participants took tetrahydrocannabinol (THC, the psychoactive component in marijuana) or placebo, and psychotic symptoms were measured.

The researchers also sought out studies in which cannabidiol or CBD was given in combination with THC, but there were not enough of these to derive significant results. CBD does not produce schizophrenia-like symptoms on its own, and some think it may have anti-psychotic effects, but findings on this topic have been mixed.

Taking THC had a large effect size on total psychotic symptoms and negative symptom severity (such as emotional flatness or avolition). It also had an effect on positive symptom severity (for example, hallucinations or delusions). The effects were larger with intravenous administration than with inhaled administration, and tobacco smokers had less severe positive symptoms.

Of four studies that included CBD, only one found that CBD reduced THC-induced psychotic symptoms.

Editor’s Note: Longer-term use of marijuana in adolescents and young adults doubles the risk of psychosis, and other data suggest that chronic use of marijuana at high doses can be associated with new onset of a diagnosis of bipolar disorder or schizophrenia. As cannabis products are being decriminalized around the US, it is worth noting some of the risks of marijuana use, particularly marijuana with a high level of THC.

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