Using Light to Improve Sleep and Depression

November 13, 2018 · Posted in Current Treatments, Risk Factors · Comment 
blue-blocking glasses

Blue-blocking glasses

At the 2018 meeting of the North Carolina Psychiatric Association, researcher Chris Aiken described the phenomenon of sleep inertia, when people are awakened from deep sleep by an alarm, rather than waking at the end of a sleep cycle, and are groggy for 15 minutes. Depressed people may stay groggy for 4 hours. A dawn simulator may help. These lights turn on gradually over the course of 30 to 60 minutes, reaching 250 lux while the patient is still asleep. Dawn simulators have worked in eight out of ten controlled clinical trials to help people with seasonal affective disorder, adolescents, and normal adults wake up more easily. They range in cost from $25 to $90 and some brands include PER2LED or LightenUp. Aiken says dawn simulators can improve depression, sleep quality, and cognition.

Evening and nighttime light: Bright lights and blue light, like the light that comes from electronic screens, can shut down the body’s secretion of melatonin, making people awake and alert in the evening when they should be getting sleepy. Dim light or glasses that filter out blue light allow increases in melatonin secretion in the evening, while bright light suppresses it. Missing this early melatonin pulse creates “night owls” who have delayed sleep onset.

Because light still reaches our eyes through our eyelids as we sleep, even low-level light during the night impairs sleep, cognition, and learning, and increases the risk of depression by a hazard ratio of 1.8 (about double the risk). A 2017 study by Kenji Obayashi in the American Journal of Epidemiology found that bedroom light above 5 lux elevated rates of depression in older adults after two years of followup. Living room light averaged around 50 lux and increased depression further.

Lux chart

A slide from Aiken’s presentation shows comparative levels of light

The treatment is turning off TVs, electronic screens, and cellphones in the evening or wearing blue-blocking glasses, which can be found for less than $10. Blue-blocking glasses can increase calmness and reduce anxiety, and even are effective in treating mania. Then, during sleep, wear an eye mask or get light-blocking blinds or curtains for windows. For a complete blackout, use blackout curtains, aluminum foil over windows, electric tape over LED lights, or try sleeping in the basement.

Aiken suggests that to re-instate healthy sleep patterns, people should institute virtual darkness from 6pm to 8am, including wearing blue-blocking glasses when out of bed. Then they should institute total darkness or wear an eye mask when in bed. When symptoms improve, this routine can gradually be shifted to begin later in the evening, such as two hours before bedtime.

Blue light filters are also available for smartphones and tablets including Apple Nightshift mode, Kindle BlueShade, and Android Twilight and Blue Light Filter.

Glasses that filter out blue light include Uvex Ultraspec 2000, 50360X ($7 on Amazon) and Uvex Skyper 351933X ($7-10 on Amazon). The website lowbluelights.com sells blue-blocking glasses from $45 and a variety of other blue-free lighting products such as lightbulbs and flashlights.

Bright light therapy for unipolar and bipolar depression: 30 minutes of bright light (7,500 to 10,000 lux) in the morning can help treat depression in unipolar and bipolar disorder and seasonal affective disorder. The effects usually take 3 to 7 days to set in, but they only last while a patient continues using the bright light in the morning. Researcher Dorothy K. Sit and colleagues found that bright light therapy in the morning sometimes caused hypomanic reactions in people with bipolar disorder, and reported in a 2018 article in the American Journal of Psychiatry that midday light therapy (from noon to 2:30pm) was also effective without this unwanted effect. However, a 2018 article by Ne?e Yorguner Küpeli and colleagues in the journal Psychiatry Research suggested that a half hour of morning light for two weeks was sufficient to bring about improvement in 81% of patients with bipolar disorder and did not cause serious side effects.

Melatonin regimen for sleep onset delay: Melatonin can be used to treat severe night-owls with a very late onset of sleep (for example, going to bed at 2 or 3am and sleeping late into the morning). Melatonin can help with sleep onset to some extent when used at bedtime, but in those with an extreme phase shift, researcher Alfred J. Lewy recommends a regimen of low dose priming with 400–500 micrograms of melatonin at 4pm and then a full dose of 3 milligrams of melatonin at midnight. The 4pm priming dose helps pull back the delayed onset of the body’s secretion of melatonin toward a more normal schedule.

Third Study Suggests Cariprazine Is Effective in Bipolar Depression

June 2, 2018 · Posted in Current Treatments, Potential Treatments · Comment 

cariprazine

The atypical antipsychotic drug cariprazine (sold under the name Vraylar in the US) is currently approved by the US Food and Drug Administration for the treatment of schizophrenia and manic or mixed episodes of bipolar disorder. Based on recent successful phase 3 trials in bipolar depression, the pharmaceutical companies that produce cariprazine, Allergan and Gedeon Richter, plan to apply for a change in FDA labeling later this year to reflect the drug’s apparent ability to treat bipolar depression as well.

While many drugs can prevent or treat mania, treating bipolar depression has typically been more of a challenge. The most recent 6-week trial of cariprazine in 493 patients showed that a dose 1.5mg/day was significantly more effective than placebo at reducing depression ratings. (A dose of 3mg/day did not show superiority over placebo as it had in previous trials of cariprazine.)

Side effects reported in the trial were mild and included restless legs, nausea, and fatigue. Five percent of those who received cariprazine discontinued the drug due to side effects, compared to three percent of those who received placebo.

The mechanism by which cariprazine improves depression is not yet clear. The drug is a dopamine partial agonist, but unlike aripiprazole (Abilify) and brexpiprazole (Rexulti), which have more potent effects on D2 receptors than on D3 receptors, cariprazine is more potent at dopamine D3 receptors. Whether this difference accounts for the positive effects in bipolar depression that aripiprazole and brexpiprazole do not have remains to be seen.

FDA Approves Lurasidone for Bipolar Depression in Children and Adolescents

April 16, 2018 · Posted in Current Treatments · Comment 

In March 2018, the US Food and Drug Administration approved the antipsychotic drug lurasidone (Latuda) for the treatment of bipolar depression in children and adolescents aged 10–17 years. Lurasidone was already approved for adults with bipolar depression, as an add-on treatment to the mood stabilizers lithium and valproate, and for schizophrenia in people aged 13 years and up.

A 6-week clinical trial in 347 youth compared lurasidone (in doses ranging from 20 to 80 mg/day) to placebo and found that those who received lurasidone showed significant improvements in depression compared to those who received placebo. The average dose was below 40 mg/day. The research by Melissa P. DelBello and colleagues was published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2017.

In the study, lurasidone was well-tolerated. Side effects included nausea, sleepiness, minimal weight gain, and insomnia. Lurasidone did not seem to affect glucose, triglycerides, cholesterol, or blood pressure.

Editor’s Note: This is the first drug to be approved for bipolar depression in this age range. This editor (Robert M. Post) has written extensively on the high incidence of childhood onset bipolar disorder in the US, and especially in the offspring of parents with bipolar disorder.
It is important to be alert to the possibilities of depression and bipolar disorder in children in the US (along with related illnesses such as anxiety, oppositional defiant disorder, and attention deficit hyperactivity disorder (ADHD)), as early-onset illness tends to have a more severe long-term course than adult-onset depression and bipolar disorder. A longer delay between the emergence of symptoms and the first treatment for bipolar disorder is also a risk factor for more severe depression, more time depressed, and a poorer outcome in adulthood.

Parents of children aged 2-12 who have mood or behavioral problems are encouraged to consider joining the Child Network at our website, bipolarnews.org (click on the tab for the Child Network). By participating in this research network, parents are able to make a weekly rating of the severity of their children’s symptoms of anxiety, depression, ADHD, oppositional behavior, and mania via the secure website. The ratings can then be shared with the child’s clinicians for easy visualization of the course of symptoms over time, which may help with treatment decisions.

Clinical Vignettes from Dr. Elizabeth Stuller

April 11, 2018 · Posted in Potential Treatments · Comment 

Dr. Elizabeth Stuller, a staff psychiatrist at the Amen clinics in Washington, DC and CEO of private practice Stuller Resettings in Baltimore, MD, provided this editor (Robert M. Post) with several interesting anecdotal observations based on her wide clinical experience with difficult-to-treat mood disordered patients.

  1. Stuller has used low-dose asenapine (Saphris), e.g. half a pill placed under the tongue, for depressed patients with alcohol use problems who have trouble getting to sleep. She has also used asenapine for rapid calming of agitated patients in her office.
  2. Stuller has also had success with the use of the atypical antipsychotic drug brexpiprazole (Rexulti) for patients with bipolar depression and low energy. She typically uses 0.5 mg/day for women and 1 mg/day for men. Stuller finds that there is little weight gain or akathisia with brexpiprazole.
  3. She has had success with the drug Nuedexta, which is a combination of dextromethorphan and quinidine and is approved for the treatment of sudden uncontrollable bouts of laughing or crying, known as pseudobulbar affect, which can occur as a result of neurological conditions or brain injuries. It is a combination of an NMDA antagonist and a sigma receptor agonist. Stuller starts with the 20mg dextromethorphan/10 mg quinidine dose once a day and increases to twice a day in week two. She finds it useful for behavioral effects of traumatic brain injury (TBI), anxiety resulting from the use of synthetic marijuana (sometimes called spice), and psychosis not otherwise specified. Stuller also finds that some patients appear to respond well to Nuedextra but not minocycline, or vice versa.

Editor’s Note: Note that these are preliminary clinical anecdotes conveyed in a personal communication, and have not been studied in clinical trials, thus should not be relied upon in the making of medical decisions. All decisions about treatment are the responsibility of a treating physician.

TDCS Effective in Bipolar Depression

February 28, 2018 · Posted in Potential Treatments · Comment 

tDCSA 2017 study in the journal JAMA Psychiatry reports that transcranial direct current stimulation (tDCS) is an effective add-on treatment for bipolar depression. In the study by researcher Bernardo Sampaio-Junior and colleagues, 59 patients taking medication for bipolar disorder and experiencing a depressive episode were randomized to receive either 10 daily half-hour sessions of tDCS (and then one every two weeks) or an inactive sham stimulation.

TDCS is a painless form of neurostimulation in which electrodes applied to the scalp provide a steady, low current of electricity that modulates neuron activity. Sampaio-Junior describes its low cost, portability and ease of use as some of its benefits. This is the first randomized, sham-controlled study of tDCS in bipolar disorder.

After six weeks of treatment, patients who received real tDCS treatment showed significantly more improvement in their depression than those who received the inactive sham stimulation. In the active group, 67.6% showed sustained response compared to 30.4% in the inactive group. TDCS was well tolerated, with skin redness at the application site the only side effect that was more common in the active group than in the sham group. Mood switching rates were similar across the two groups.

The research was completed as part of the Bipolar Depression Electrical Treatment Trial (BETTER) taking place in Brazil. The group of participants was 68% female with a mean age of 45.9 years. Sixty-one percent of participants had bipolar I disorder while the remainder had been diagnosed with bipolar II.

An Inflammatory State Impedes Treatment for Bipolar Disorder

January 4, 2018 · Posted in Current Treatments · Comment 

A 2017 study by in the Journal of Clinical Psychiatry links inflammation to a poor antidepressant response in bipolar disorder. Many previous studies have found that elevated inflammatory markers are common in mood disorders, and that an inflammatory state seems to prevent response to certain therapies.

Researcher Francesco Benedetti and colleagues report that high levels of inflammatory cytokines (a type of small proteins) predicted a worse response to treatment with sleep deprivation and light therapy for bipolar depression. This treatment typically brings about a rapid antidepressant response.

Benedetti and colleagues measured 15 immune-regulating compounds in 37 patients who were experiencing an episode of bipolar depression and 24 healthy volunteers. Among those participants with bipolar disorder, 84% had a history of non-response to medication. Twenty-three of the 37 patients, or 62%, responded to the sleep deprivation/light therapy combination. Those who did not had higher levels of five cytokines: interleukin-8, monocyte chemoattractant protein-1, interferon-gamma, interleukin-6, and tumor necrosis factor-alpha.

Body mass index was correlated with cytokine levels and also reduced response to the treatment.

The finding supports a link between the immune system and mood disorders. Evaluating a patient’s level of inflammation may, in the future, allow doctors to predict the patient’s response to a given therapy. Patients with high levels of inflammation might benefit most from treatments that target their immune system.

Arthritis Drug Celecoxib May Improve Bipolar Depression When Paired with Escitalopram

March 13, 2017 · Posted in Potential Treatments · Comment 

celecoxib combined with escitalopram for bipolar depression

A new study suggests that for people with bipolar depression, the anti-inflammatory drug celecoxib (Celebrex), typically used to treat arthritis, can boost the effectiveness of the antidepressant escitalopram (Lexapro).

In the 8-week study by researcher Angelos Halaris and colleagues, adults with bipolar depression were randomly assigned to one of two groups. The first group received the selective-serotonin reuptake inhibitor (SSRI) antidepressant escitalopram plus celecoxib to target inflammation. The second group received just the antidepressant escitalopram and a placebo.

By the end of the study, 78% of the group taking the anti-arthritis drug had seen major improvement in their depression, with 63% reporting that it had lifted completely. Meanwhile in the placebo group, only 45% reported major improvement, and 10% reported remission.

The group that received celecoxib with their escitalopram also began seeing improvement within one week of beginning treatment, instead of after four to six weeks, which is typical of antidepressant treatment.

Researchers think depression creates an immune response leading to chronic inflammation, which can upset the balance of neurotransmitters in the brain and make antidepressants less effective. Halaris suggests that reducing this inflammation with a drug like celecoxib can make antidepressants more effective.

The research was presented at the Fifth International Congress on Psychiatry and the Neurosciences and has not yet been published.

Vitamin D Supplementation May Not Be Effective in Bipolar Depression, But Is Still Worth Doing

January 27, 2017 · Posted in Potential Treatments · Comment 

vitamin DIn some studies, vitamin D supplementation (1,500 IU/day) has been found to improve unipolar depression. Recently, researchers led by Wendy K. Marsh found that compared to placebo, 12 weeks of vitamin D3 supplementation (5,000 IU/day) did not produce greater improvement in depressive symptoms. The study, presented at the 2016 meeting of the Society of Biological Psychiatry, included 33 adult participants whose vitamin D levels remained deficient throughout the study.

Editor’s Note: Caution is urged in interpreting this small study, especially because the participants did not achieve healthy levels of vitamin D.

Low levels of vitamin D are common in children and adults with bipolar disorder. Future research may explore whether raising vitamin D levels to healthy levels has a beneficial effect on mood. There are many other benefits to vitamin D supplementation. It can improve cognition, regulate calcium and phosphorus absorption, and maintain healthy bones and teeth. It may also protect against diseases such as cancer, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. Improved cardiovascular health is also a possible benefit of vitamin D supplementation.   

Treatment with Hormone EPO Improved Cognition in People with Unipolar and Bipolar Disorder

January 10, 2017 · Posted in Potential Treatments · Comment 

improved cognition

People with unipolar depression and bipolar disorder may experience cognitive difficulties, even when they’re not currently depressed. In a study published in the journal European Neuropsychopharmacology in 2016, researchers led by Caroline Vintergaard Ott determined that treatment with the hormone erythropoietin (EPO) may help.  EPO is produced in the kidney and increases the production of hemoglobin and red cells.

Seventy-nine participants with unipolar or bipolar disorder were randomized to receive infusions of either EPO or a saline solution once a week for eight weeks. By the end of the study, those who received EPO showed significant improvements in the speed of their complex cognitive processing compared to those who received saline. EPO is known to induce the production of red blood cells. The improvements in processing speed lasted for at least another six weeks after red blood cell production would have normalized.

Those participants who received EPO not only had improved scores on tests of processing speed, they also reported fewer cognitive complaints. The EPO treatment was most likely to be effective in participants who had more impaired cognition at the beginning of the study.
In previous research by the same research group presented by Kamilla W. Miskowiak at the 2014 meeting of the International Society of Bipolar Disorders, EPO also improved sustained attention and recognition of happy faces.

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.

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