FDA Approves Treatment for Tardive Dyskinesia

May 26, 2017 · Posted in Current Treatments · Comment 

facesA new drug valbenazine (trade name Ingrezza) has been approved by the US Food and Drug Administration for the treatment of tardive dyskinesia. Tardive dyskinesia, a side effect of long-term use of antipsychotic medication, consists of involuntary movements of the tongue, face, torso, arms, and legs. It can interfere with walking, talking, and breathing.

The approval followed 20 clinical trials of valbenazine that included a total of more than 1000 participants who had symptoms of tardive dyskinesia in addition to schizophrenia, schizoaffective disorder, or bipolar disorder.

In a 2017 article in the American Journal of Psychiatry, researcher Robert A. Hauser and colleagues reported that patients who received 80 mg/day of valbenazine had a significant reduction in tardive dyskinesia symptoms after six weeks compared to those who received placebo. Participants who received 40 mg/day of valbenazine also had reductions in symptoms, although not as dramatic as with the higher dose.

Serious side effects of valbenazine include sleepiness and lengthening of the QT interval, which can increase heart arrhythmias. The FDA notes that people who already have abnormal heartbeats due to a long QT interval should not take valbenazine. In addition, people taking the drug should avoid driving or operating heavy machinery until they know how valbenazine affects them.

Lithium Responders and Non-Responders Have Different Neuron Characteristics

May 22, 2017 · Posted in Current Treatments · Comment 
after hyperpolarization

After hyperpolarization (via Wikimedia Commons)

A 2017 study in the journal Molecular Psychiatry suggests that by observing the neurons of a person with bipolar disorder, you can predict whether they will respond to lithium treatment. The drug is effective in approximately 30% of those to whom it is prescribed.

Researchers led by Shani Stern and Renata Santos used stem cell research to analyze neurons from people with bipolar disorder and healthy controls.

People with bipolar disorder shared some neuron features, namely a large, fast after-hyperpolarization (a phase in which the cell’s membrane changes), which is followed by a resting period before the neuron can fire again. The large, fast hyperpolarization in people with bipolar disorder speeds up this cycle, leading to fast and sustained neuron firing. This replicated previous findings by the same researchers, which found that people with bipolar disorder are more sensitive to stimuli. In people with bipolar disorder, the threshold for a neuron to fire drops with each subsequent after-hyperpolarization.

Chronic lithium treatment reduced this hyperexcitability in some patients—and these were the patients who had a good response to lithium treatment.

Among the study participants with bipolar disorder, there were differences in the neuron profiles of those who responded well to lithium versus those who did not.

Stern and colleagues programmed a computer to recognize the electrophysiological features of neurons from lithium responders and non-responders. The computer could then analyze the neurons of a patient whose response to lithium was unknown and predict with a greater than 92% success rate whether that patient had responded well to lithium treatment.

Adherence to Antidepressants Associated with Lower Mortality

April 28, 2017 · Posted in Course of Illness, Current Treatments · Comment 

man taking an antidepressant

A large study from Israel suggests that over a 4-year period, people who regularly took their prescribed antidepressants were less likely to die of any cause during that period.
The study, published in the Journal of Clinical Psychiatry in 2016, used data from an Israeli health provider that covers 53% of the nation’s population. It included 251,745 patients aged 40 and up who filled a prescription for an antidepressant at least once between 2008 and 2011.

Researchers led by Amir Krivoy looked at how much of the time people actually filled their prescriptions. Patients who filled their prescriptions more of the time were less likely to die during the study period than those who did not fill their prescriptions regularly.

Editor’s Note: This study by Krivoy and colleagues provides more evidence of the benefit of long-term antidepressants. People who have had two or three episodes of unipolar depression should consider long-term prevention with antidepressants over the course of their lifetime, in the way that people take blood pressure medications long-term to prevent heart attacks. In addition to lowering mortality, antidepressants also reduce the rate of relapse by 75% compared to placebo. More time on antidepressants also preserves hippocampal volume with aging.

Therapy Reduces Relapses, Promotes Medication Adherence

April 19, 2017 · Posted in Current Treatments · Comment 

woman speaking with therapist

A 2017 meta-analysis published in the British Journal of Psychiatry indicates that psychosocial interventions were linked to reduced relapse rates, better adherence to medication, and other benefits in people with bipolar disorder. The meta-analysis by researcher Mary Lou Chatterton and colleagues evaluated data from 41 studies with a total of 3,119 participants. The studies examined psychosocial interventions such as cognitive-behavioral therapy, psychoeducation, and family-focused therapy compared to treatment as usual.

Chatterton and colleagues found that interventions that targeted family members who act as caregivers reduced manic and depressive relapse rates. Combined psychoeducation and cognitive-behavioral therapy was more successful than any other intervention, and had a large effect in reducing symptoms of mania. This combination also improved general functioning. Psychoeducation alone and in combination with cognitive behavioral therapy reduced medication non-adherence. Unfortunately, no intervention reduced depressive symptoms.

Mood Stabilizers with Atypical Antipsychotics Reduce Relapses Compared to Mood Stabilizers Alone or with Typical Antipsychotics

April 18, 2017 · Posted in Current Treatments · Comment 

Retired mature man sitting on couch and looking at camera.

An Israeli study reports that treatment with mood stabilizers and atypical antipsychotics reduces bipolar relapses compared to treatment with mood stabilizers alone or mood stabilizers combined with typical antipsychotics. The study, by Eldar Hochman and colleagues in the journal Bipolar Disorders, compared one-year hospitalization rates after patients with bipolar disorder were discharged from the hospital following a manic episode. All of the 201 discharged patients were prescribed a mood stabilizer (lithium or valproate), and some were also prescribed an antipsychotic, either atypical or typical.

Those participants who received the combination of a mood stabilizer and an atypical antipsychotic had re-hospitalization rates of 6.3% compared to 24.3% of those who received mood stabilizers alone and 20.6% of those who received mood stabilizers with a typical antipsychotic.

While the study did not determine which treatment is best for ongoing maintenance treatment of bipolar disorder, it does suggest that the combination of mood stabilizers and atypical antipsychotics can reduce hospitalizations during the one-year period following a manic episode.

Lithium May Reduce Cancer Risk

April 17, 2017 · Posted in Current Treatments · Comment 

smiling senior asian man

New research suggests that cumulative exposure to lithium may correlate with reduced cancer risk in patients with bipolar disorder. A 2016 article by Yi-Hsin Yang and colleagues in the British Journal of Psychiatry reports findings from a Taiwanese population database study of 4,729 adult patients with bipolar disorder, 115 of whom were diagnosed with cancer. Those who had been prescribed lithium (with or without anticonvulsants) had lower rates of cancer (1.96%) than those who received only anticonvulsants (2.65%).

Incidence of cancer was higher among the patients with bipolar disorder than the general population in the study. Other studies have indicated that cancer risk is higher among people with bipolar disorder than those without.

Those people who took a recommended maintenance lithium dose for 215 days or longer had a 44.8% lower risk of cancer than those who took only anticonvulsants.

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.

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