Lithium May Work by Restoring Dendritic Spines

April 14, 2017 · Posted in Current Treatments, Neurobiology, Theory · Comment 
spines on a dendrite

spines on a dendrite

New research on mice clarifies lithium’s effects on neurons and suggests how it can lead to improved symptoms. Dendrites are the long projections on neurons that seem to reach out to form synapses with other neurons. The surface of these dendrites is covered in mushroom-shaped spines that help create these synaptic connections. A 2016 article by research Ben Cheyette and colleagues in the journal Molecular Psychiatry reports that in mice with a genetic mutation common to people with autism, schizophrenia, and bipolar disorder, lithium restored healthy numbers of the mushroom-shaped spines. The lithium treatment also reversed symptoms such as lack of interest in social interactions, lack of motivation, and anxiety in the mice.

Cheyette and colleagues first identified a genetic mutation that affects signaling in what is known as the brain’s Wnt pathway. The mutation, while rare, is 80% more common in people with bipolar disorder, autism, and schizophrenia than in people without these disorders.

When the mice were given a similar mutation, they exhibited symptoms such as anxiety, decreased sociability, and lack of motivation. They also had reduced numbers of dendritic spines and impaired Wnt signaling.

Lithium can improve Wnt signaling by blocking an enzyme called GSK-3 beta that impairs the signaling.

Treating the mice with lithium restored their dendritic spines and improved their behavior.

Wnt signaling and dendritic spines may offer the key to lithium’s success in treating a variety of psychiatric disorders in people.

Only Fluoxetine is More Effective Than Placebo for Children and Adolescents with Depression

April 11, 2017 · Posted in Current Treatments · Comment 

Young Latina woman showing white medication tabletIn a meta-analysis published in 2016, researchers Andrea Cipriani, Xinyu Zhou, and colleagues reported that many antidepressants are not effective in children and adolescents. Fluoxetine alone was more effective than placebo. Other antidepressants also caused high study drop-out rates compared to placebo.

In an article published in the journal The Lancet, Cipriani, Zhou, and colleagues analyzed 34 randomized, controlled clinical trials of antidepressants in children and adolescents. These trials included a total of 5,260 participants and 14 different antidepressants.

The researchers determined that much of the evidence was of a low quality. Only fluoxetine was statistically significantly more effective than placebo. Fluoxetine was also more tolerable to patients than duloxetine or imipramine. Patients who received imipramine, venlafaxine, or duloxetine were more likely to drop out of studies due to adverse events compared to patients who received placebo.

The authors suggest that prescribing antidepressants to children or adolescents may not necessarily be beneficial, and that fluoxetine is probably the best option to consider.

Editor’s Note: It may be best to use caution when prescribing antidepressants to children or adolescents. First, these data that suggest that many antidepressants are ineffective in young people. In addition, depression in children and adolescents may be a sign of bipolar disorder, and antidepressant use may cause activation or switching into mania in vulnerable patients.

While there is a warning about using antidepressants in young people because of the risk of increased suicidal ideation, the actual suicide rate in young populations decreases when these patients take antidepressants and cognitive behavioral therapy. Psychotherapy should be a high priority. Other safe adjunctive approaches might include omega-3 fatty acids, N-acetylcysteine, vitamin D3, and folic acid. Evidence for the efficacy of rTMS in young people is also positive and growing.

Inflammation Predicts Poor Response to Fluoxetine in Kids

April 10, 2017 · Posted in Current Treatments · Comment 

Nurse taking blood sample from patient at the doctors office

Inflammation upsets the balance of neurotransmitters in the brain and can make antidepressants less effective. In new research by Maya Amitai and colleagues, children and adolescents were less likely to respond to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine if they had high levels of inflammation measured in the blood.

Amitai’s study included 41 patients between the ages of 9 and 18. They met criteria for a diagnosis of either major depression or an anxiety disorder. The participants were treated with the SSRI fluoxetine for eight weeks. Those with high levels of the inflammatory markers tumor necrosis factor (TNF) alpha, interleukin-6, and interleukin 1 beta were less likely to respond to the antidepressant treatment. The research was published in the Journal of Child and Adolescent Psychopharmacology in 2016.

Editor’s Note: These findings parallel those from studies of adults, suggesting that inflammation can predict poor response to antidepressants in all age groups.

Preventative Treatment Should Begin After First Manic Episode

March 8, 2017 · Posted in Current Treatments · Comment 

teen with bipolar disorder

Evidence from multiple studies has indicated the importance of beginning preventative treatment, particularly with lithium, early in the course of bipolar disorder. A 2016 comprehensive literature review by researcher Katie Joyce and colleagues in the International Journal of Bipolar Disorders concluded that psychoeducation and medication are more effective in bipolar disorder when applied in earlier stages of the illness rather than later stages.

Several  studies suggest that treatment for bipolar disorder should be started specifically after the first manic episode.

A 2014 study by researcher Lars Kessing and colleagues in the British Journal of Psychiatry examined 4,700 patients treated with lithium in Denmark. Kessing and colleagues found that those who started treatment after one manic episode were less likely to find lithium ineffective than those who started later.

Another study by researcher Michael Berk and colleagues presented at the International Society for Bipolar Disorders found that after a first manic episode, a year of treatment with lithium was much more effective on all measures of outcome, including mania and depression ratings, brain imaging, and neuropsychological functioning, than a year when patients were randomized to quetiapine (Seroquel).

Researcher Lakshmi Yatham and colleagues presented research at the International Society for Bipolar Disorders showing that patients recovered from the neuropsychological deficits associated with a first episode of mania if they were well treated and had no further episodes, while those who had new episodes did not return to their baseline capabilities. This suggests that early treatment that prevents future episodes helps maintain a healthy brain.

Kessing and colleagues previously reported in the British Journal of Psychiatry in 2013 that patients randomized to two years of treatment in an outpatient clinic specializing in mood disorders following a first hospitalization for mania had 40% fewer recurrences of bipolar episodes over the next six years than those who received treatment as usual. These data indicate that early treatment, which may include psychotherapy, medications, mood charting (i.e. keeping a daily record of symptoms) and illness education, can improve the long-term course of illness. Lithium is often a key component of such treatment.

Editor’s Note: This type of intensive, ongoing treatment is not the norm after a first manic hospitalization in the United States, but it should be. Given the new data on the impact of starting lithium after a first episode of mania, and lithium’s superiority over quetiapine in the year following a first episode, lithium treatment should be standard following a diagnosis of bipolar disorder.

In the past, sometimes doctors have recommended waiting until a patient has had multiple episodes of mania before beginning preventative treatment with lithium. This now appears to be a mistake.

Lithium protects against depressive as well as manic recurrences, and there is also evidence that it increases hippocampal and cortical volume, helping prevent cognitive deterioration in those with mild cognitive impairment. Lithium is also the most effective mood stabilizer for preventing suicide, and it increases the length of telomeres (caps on the end of DNA strands), thus preventing a wide range of medical and psychiatric illnesses. Lithium may need to be combined with other drugs to achieve a complete remission, but using it after a first mania is a good place to start.

Psychotherapy Improved Depression, Reduced Inflammation

December 21, 2016 · Posted in Current Treatments · Comment 

supportive expressive psychodynamic therapy

A recent study shows that psychotherapy can not only improve depression symptoms, but may also reduce the inflammation that often accompanies them.

Researcher Jean Pierre Oses and colleagues randomly assigned participants with depression to receive Supportive-Expressive psychodynamic therapy, which is designed to help patients understand conflictual relationship patterns, or an alternative therapy. Among the 47 participants who received Supportive-Expressive therapy, depression improved significantly after 16 sessions, and blood levels of the inflammatory markers interleukin-6 and TNF alpha also dropped.

The research was presented at the 2016 meeting of the Society of Biological Psychiatry.

Lithium Increases Cortical Thickness in People with Bipolar Disorder

November 28, 2016 · Posted in Current Treatments · Comment 

superior frontal gyrusRecent studies have indicated that bipolar disorder is associated with changes to brain volume, including thinning of the cortex. In research presented at the 2016 meeting of the Society of Biological Psychiatry, researcher Noha Abdel Gawad reported that four weeks of lithium treatment increased cortical thickness in the left superior frontal gyrus. This is the third replication of this finding.

Other research has established that lithium treatment also increases the volume of the hippocampus in people with bipolar disorder. Together the findings provide strong evidence that lithium treatment protects neurons and can reverse brain changes associated with bipolar disorder.

Lithium Lengthens Telomeres

November 25, 2016 · Posted in Current Treatments · Comment 

telomereTelomeres are repeated DNA sequences that sit at the end of chromosomes and protect the DNA as it is replicated. Depressive episodes and age can reduce the length of telomeres. Lithium treatment increases telomere length. At the 2016 meeting of the Society of Biological Psychiatry, researcher Martin Schalling reported that the longer a patient takes lithium, the more their telomere length increases.

According to Schalling, people who respond well to lithium treatment show greater increases in telomere length than those who respond poorly to lithium.

While some cancers are associated with long telomeres, lithium use has not been found to increase cancer risk. In fact, lithium treatment can decrease the risk of certain cancers of the gastrointestinal, respiratory, and endocrine systems.

Meta-Analysis Shows Anti-Inflammatory Treatments Improve Bipolar Depression

November 22, 2016 · Posted in Current Treatments · Comment 

anti inflammatory treatments for bipolar depressionIt has been clear for some time that depression and inflammation are linked. This has led researchers to explore a variety of anti-inflammatory agents to treat depression. A meta-analysis of studies examining anti-inflammatory treatments for bipolar depression was published in the journal Bipolar Disorders in 2016.

Researcher Joshua D. Rosenblat and colleagues identified eight randomized controlled trials that met their criteria for anti-inflammatory treatments of bipolar disorder. These treatments included nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen and aspirin), omega-3 fatty acids, the antioxidant N-acetylcysteine, and pioglitazone (used to treat diabetes). Overall, the anti-inflammatory treatments had a moderate and statistically significant antidepressant effects. No serious side effects were reported, and the anti-inflammatory treatments did not cause a switch into mania in any of the participants.

The diversity of the anti-inflammatory treatments reviewed in this meta-analysis limit the extent to which it can be interpreted, but it is clear that more research on anti-inflammatory treatments for bipolar depression is needed. An open question is whether patients with particularly elevated levels of inflammatory markers in their blood would respond better to these anti-inflammatory treatments.

Galantamine Did Not Improve Cognitive Deficits in People with Bipolar Disorder

November 18, 2016 · Posted in Current Treatments · Comment 

cognitive deficits

In a recent study by researcher Dan V. Iosifescu and colleagues, the drug galantamine, which is used to treat dementia, did not improve cognitive function in euthymic people with bipolar disorder. The drug had done so in earlier studies. Seventy-two participants with bipolar disorder that was in remission were randomized to receive either a placebo or galantamine extended release for a period of two weeks. Doses of galantamine ranged from 8 to 24 mg/day.

The participants took several tests of attention and memory over the course of the study. After 16 weeks of treatment, those taking galantamine did not show significant improvements in functioning compared to those who received placebo.

This research was presented at the 2016 meeting of the Society of Biological Psychiatry.

Inflammation Linked to Non-Response to Antidepressants

November 17, 2016 · Posted in Current Treatments · Comment 

antidepressant non-response and inflammation

In a symposium on inflammation’s role in psychiatric disorders at the 2016 meeting of the Society of Biological Psychiatry, researcher Carmine Pariante reviewed the considerable literature indicating that major depression is often associated with measures of inflammation. Depression has been linked to elevated blood levels of the inflammatory proteins interleukin-1, interleukin-6, TNF alpha, and c-reactive protein, with about one-third of depressed patients having an elevated level of at least one of these proteins. People with elevated inflammatory markers are also less likely to respond to traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs).

Pariante reported that in depressed people, interleukin-6 is also elevated in cerebrospinal fluid in addition to blood, suggesting that inflammation in depression extends to the central nervous system. Increased secretion of interleukin-6 has been linked to depressive behaviors in mice exposed to stress.

There is some hope that anti-inflammatory treatments can help patients who do not respond to traditional antidepressant treatment. Some anti-inflammatory medications that may eventually be used to treat depression with inflammation include the COX-1 inhibitor aspirin, the COX-2 inhibitor celecoxib (Celebrex), or the antibiotic minocycline. Each of these approaches gained some support in preliminary clinical trials, but it has not yet been established that these anti-inflammatory treatments produce a better response in people with elevated inflammatory markers.

« Previous PageNext Page »