The Need for Psychotherapy for Bipolar Disorder
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Greg Murray gave a talk on effectiveness of multiple types of psychotherapy for bipolar disorder and suggests that the choice be designed for each individual.
He describes 10 core elements of each type of therapy. These included dealing with:
- 1. Knowledge, acceptance, and adherence
- 2. The presence of anxiety in some 90% of patients
- 3. Suicidality and crisis management
- 4. Skills: monitoring, relapse prevention, life time events, recognition of early symptoms
- 5. Identity, cognitive restructuring, dealing with stigma, train action and achievement, confronting perfectionism, CBT
- 6. Sleep and circadian rhythms
- 7. Trauma, child adversity, PTSD
- 8. Emotion regulation
- 9. Relationships: social, family, occupational roles (family or group)
- 10. Substance use and avoidance, access, motivational interviewing, impulsivity
Positive Effects of Low-Dose Lithium (LDL)
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Rebecca Strawbridge of the Institute of Psychiatry, Psychology & Neuroscience, King’s College London reported on 18 articles that were examined and grouped according to outcome domain (cognition, depression, mania, and related constructs e.g., suicidality). Significant benefits (versus placebo) were identified for attenuating cognitive decline, and potentially as an adjunctive therapy for people with depression/mania. Across studies, LDL (~serum level ?0.6 mmol/L) was reported to be safe.
Patterns of Pharmacotherapy for Bipolar Disorder
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Balwinder Singh of the Mayo Clinic College of Medicine reported on “10,351 individuals from North America (n=3,985), Europe (n=3,822), and Australia (n=2,544), predominantly with cross-sectional data (80%)….They found that “Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were most prescribed. Lithium was prescribed in 29% of patients, primarily in Australian (31%) and European (36%) cohorts.” Lithium is remarkedly underutilized in North American cohorts.
Cognitive Function and White Matter Integrity in Individuals With Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Jennifer McDowell reported that they found “significantly reduced FA (fractional anisotropy) values in 85 bipolar probands compared to 66 controls” in multiple (n=8) white matter tracts. There were significantly lower scores in bipolar probands compared to controls on composite scores, ( p = 0.007), verbal fluency, ( p < 0.001), and symbol coding, (p = 0.023). They concluded that: “ Impacted connectivity in critical fiber tracts may be key to understanding the neural underpinnings of deficits, like cognition, observed in this clinical population.”
Editors note: It is of interest that lithium has been shown to normalize some white matter abnormalities in youngsters and help preserve cognitive function in older individuals. On this and many other accounts, way too little lithium is being used in the treatment of patients with bipolar disorder. Lithium not only increases neurogenesis (new grey matter neurons) and hippocampal volume, but also has positive effects on white matter tracts and even increases the length of one’s telomeres (which keeps you more healthy). In other ungrammatical words, “If your brain is not connected right, it don’t work right.”
LITHIUM’S AMAZING DIVERSITY OF ASSETS
Editor’s Note: Lithium is vastly underutilized. There is wide spread ignorance about its many assets and misconceptions about its few side effects. Here is an update that should be of interest to potential users, family members, and clinicians.
Lithium:
- Prevents unipolar and bipolar depression
- Augments effects of antidepressants in unipolar depression
- Potentiates the effects of atypical antipsychotics in treating mania and depression
- Reduces inflammation
- Normalizes some aspects of cardiovascular risk
- Normalizes secretions for monocytes and leukocytes
- Increases neurogenesis, BCl-2, and hippocampal and thalamic volumes
- The increases in neuroprotective factors occurs at brain levels below typical therapeutic dosages
- Protects against memory deterioration
- Lowers dementia risk in old age
- Reduces suicide clinically and at minute concentrations in the water supply
- Lengthens telomeres and increases longevity
- Reduces size of lesions in models of stroke, AIDS, and Huntington’s chorea
- Normalizes circadian rhythms
- Reduces manic-like behavior induced by clock gene mutations
- Prevents calcium currents and increased firing rate in stem cells from bipolar patients
- Induces minimal to no weight gain on long term follow up
- Does not increase risk of kidney failure when given at blood levels of .6 to .8 blood levels
- Protects against spine and hip osteoporosis
Conclusion: With so many assets and so few liabilities, physicians and patients should reconsider the benefits of lithium and use it more often, not only in the few who respond to it as a monotherapy, but as a adjunct to the many other treatments of bipolar disorder. This should be a “no brainer” as lithium will very likely help some have fewer problems from their illness and may even help them live longer.
Many of these points are summarized in the open access publication: Robert M Post, The New News About Lithium: An Underutilized Treatment in The United States, Neuropsychopharmacology accepted article preview 4 October 2017; several new updates have been added from the International Society on Bipolar Disorders meeting, Chicago, June, 2023.
Effectiveness of Repeated Ketamine Infusions for Treatment Resistant Bipolar Depression
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Farhan Fancy, of the University of Toronto, gave 66 highly treatment resistant (unselected) bipolar I or II patients four sub-anesthetic doses of IV ketamine (0.5-0.75mg/kg) over a two-week period. They saw significant reductions in depression, anxiety, suicidality, and disability. Response rates were 35% and remission rate was 20%. “Infusions were generally well tolerated with treatment-emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis.”
“Pharmacotherapy of Bipolar Depression”
Roger McIntyre gave a talk on the “Pharmacotherapy of Bipolar Depression” at the International Society for Bipolar Disorders Conference in Chicago, June 22-25, 2023
He pointed out that, contrary to the many approved agents for mania, there were few FDA-approved drugs for depression in patients with Bipolar Disorders. These approved drugs included: cariprazine (Vraylar); lumateperone (Caplyta); lurasidone (Latuda); quetiapine (Seroquel); and the olanzapine-fluoxetine combination (Symbyax). Other non-approved agents include: lithium, lamotrigine, antidepressants, MAOIs, pramipexole, carbamazepine, ketamine, bupropion+dextromethorphan, amantadine, memantine, and possibly minocycline and celecoxib. Surprisingly, more than 3,000 bipolar depressed patients have been reported to be taking ketamine and that this was not associated with the induction of hypomania or mania.
McIntyre reported on the antidepressant (AD) effects of intra-nasal (i.n.) insulin. The insulin receptor sensitizer metformin had AD effects, but only in those who converted to insulin sensitivity.
McIntyre reported on the mixed effects of the GLP-1 agonists in the prevention of depression (Cooper et al J. Psychiatric Res, 2023). This is of interest in relationship to the bidirectional relationship of diabetes mellitus and depression.
Liraglutide appeared to have an anti-anhedonia effect. Semaglutide had AD and antianxiety effects in animal models of depression.
Recent studies have explored the antidepressant effect of psilocybin. Small studies have indicated that it has rapid onset of AD effects, and, in contrast to ketamine where rapid onset AD and anti-suicidal effects are short lived, the AD effect of psilocybin may be more prolonged.
Ketamine repairs structure and function of prefrontal cortical neurons via glutamate NMDA receptor blocking action, while psilocybin and other psychedelics act via stimulating 5HT2A receptors. One single case study suggested that blocking 5HT2A receptors with trazodone could achieve a rapid onset of AD effects of psilocybin without the psychedelic effects, a very interesting finding that requires replication.
Early Antidepressant Use is Associated with Rapid Cycling Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
A.C. Courtes and Jair Soares reported that “Antidepressants were prescribed as the first psychiatry medication in 74/114 (65%) of BD patients.” This and alcohol use disorder were independent predictors of rapid cycling.
Risk of Attempted or Completed Suicide in Borderline Personality Disorder: Reduced with ADHD meds; Increased with Benzodiazepines
Johannes Lieslehto et al 2023 reported in JAMA New. Open on the comparative effectiveness in 22,601 individuals with BPD that “ADHD medication was the only pharmacological treatment associated with reduced risk of suicidal behavior among patients with BPD. Conversely, the findings suggest that benzodiazepines should be used with care among patients with BPD due to their association with increased risk of suicide.” Mood stabilizers had no effect while antipsychotics minimally and antidepressants moderately increased risk of suicide attempts or completed suicide.
The Cognitive Effects of Electroconvulsive Therapy in Community Settings
Harold Sackeims’ review in Neuropsychopharmacology, 32, 244-254 (2007) remains one of the best updates indicating that the cognitive effects of Electroconvulsive Therapy (ECT) are not always benign. They followed 347 patients from seven facilities in New York city and tested them after their last session of ECT and then again 6 months later. They reported that “Electrical waveform and electrode placement had marked cognitive effects. Sine wave stimulation resulted in pronounced slowing of reaction time, both immediately and 6 months following ECT. Bilateral (BL) ECT resulted in more severe and persisting retrograde amnesia than right unilateral ECT. Advancing age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits. Thus, adverse cognitive effects were detected 6 months following the acute treatment course. Cognitive outcomes varied across treatment facilities and differences in ECT technique largely accounted for these differences. Sine wave stimulation and BL electrode placement resulted in more severe and persistent deficits.”
Editors note: This is why it is important to recommend right unilateral ultra brief pulse (RUUBP) ECT both for acute and continuation treatment if necessary. Continuing RUUBP ECT rather than converting to bilateral ECT would appear to be preferable.
