Brain-derived neurotrophic factor (BDNF) is a protein that protects neurons and aids with learning and memory. BDNF levels are low in people with depression, and every type of antidepressant treatment increases BDNF, including different types of medications, electro-convulsive therapy, repeated transcranial magnetic stimulation (rTMS), exercise, atypical antipsychotic drugs used to treat bipolar depression, omega-3 fatty acids, and ketamine. New research shows that sleep deprivation, which is sometimes used to rapidly improve depression, also increases BDNF.
A study by researcher Anne Eckert and colleagues found that partial sleep deprivation (preventing sleep only during the second half of one night) increased BDNF levels in the blood the following day. Those participants who responded well to the sleep deprivation were found to have BDNF levels that fluctuated more throughout the day before the sleep deprivation compared to participants who did not respond well to the sleep deprivation, whose BDNF levels were relatively stable.
The research, which was presented at a scientific meeting in 2015, suggests that sleep deprivation in depressed patients increases BDNF, and that such increases are an important function of any antidepressant treatment.
Lurasidone (Latuda) has been approved by the US Food and Drug Administration (FDA) for the treatment of bipolar depression. A new study indicates that lurasidone is also effective in those with unipolar depression complicated by a few manic features, i.e. mixed depression, which is often more severe and less responsive to traditional antidepressants than traditional unipolar depression.
At a 2015 scientific meeting, Andrew Nierenberg and colleagues presented the results of a six-week study comparing 20–60 mg of lurasidone to placebo in about 200 depressed patients who had some manic symptoms. Lurasidone significantly improved unipolar depressive symptoms in addition to the mixed manic symptoms.
At baseline, the patients’ manic symptoms included: flight of ideas/racing thoughts in 66.8% of the participants, pressured speech in 61.1%, decreased need for sleep in 40.8%, increased energy or activity in 28.0%, elevated or expansive mood in 18.0%, increased or excessive involvement in pleasurable activities in 15.6%, and inflated self-esteem or grandiosity in 6.6%.
Lithium is one of the most effective medications for bipolar disorder, but it has other benefits as well. At a 2015 scientific meeting, Ronald Fieve reported that among 1021 psychiatric outpatients, 570 who received long-term lithium treatment for their psychiatric illnesses had a significantly lower likelihood of certain medical conditions compared to the other outpatients who did not receive lithium therapy. The medical conditions that lithium made less likely were seizures, amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, dementia, and heart attack.
It is not yet know how lithium decreases these medical conditions. It may be by increasing the length of telomeres. Telomeres are repeated DNA sequences that sit at the end of chromosomes and protect them during cell replication. Telomeres get shorter with aging and with stressors or psychiatric illnesses. Lithium directly increases the enzyme telomerase, which maintains telomere length. This may be one reason lithium use provides some protection from seizures, heart attacks, and other conditions.
Benzodiazepines are a class of drugs that became widely used in the 1970s for their ability to reduce panic, anxiety, and insomnia. Some also functioned as anticonvulsants, reducing seizures. They are considered “downers,” with sedating qualities.
New research shows that benzodiazepine use, particularly long-term use, comes with risks such as increased mortality and mood instability.
At a 2015 scientific meeting, researcher Jari Tiihonen reported that among 21,492 patients with schizophrenia in Sweden, benzodiazepine use was associated with increased mortality, while antidepressant and antipsychotic use decreased mortality.
At the same meeting, researcher Cristina Albott reported that benzodiazepines may interfere with the rapid onset of antidepressant effects usually brought about by intravenous treatment with the drug ketamine.
In 2010, researcher Roy Perlis reported in the Journal of Clinical Psychiatry that in STEP-BD, a large study of people with bipolar disorder, benzodiazepine use was associated with an increased risk of recurrence of mood episodes.
Editor’s Note: Benzodiazepines can also exacerbate symptoms of post-traumatic stress disorder (PTSD) and regular use can lead to a decrease in lifespan. It now seems as though there are many reasons to exercise caution in the use of these drugs.
Studies published in 2015 and 2016 have established that generic versions of the anti-convulsant lamotrigine are bioequivalent to the name-brand drug (Lamictal) and to each other. Lamotrigine is used to treat epilepsy and is also prescribed for the prevention of bipolar depression.
An article by T.Y. Ting and colleagues in the journal Epilepsia in 2015 established that generic lamotrigine works similarly enough to the name brand drug that patients with epilepsy could be switched from one drug to the other without worsening seizures. More recently, M.D. Privitera and colleagues reported in the journal Lancet Neurology that different generic versions of lamotrigine were bioequivalent. No significant changes in seizure frequency or other negative outcomes were reported.
These studies show that generic versions of lamotrigine have the same anticonvulsant effectiveness as the original drug. The same should also be true for lamotrigine’s effectiveness in preventing bipolar depression.
Studies have shown that therapy can be helpful for people with bipolar disorder. In a 2016 article in the British Journal of Psychiatry, researchers led by M. Oud described the findings of their systematic review of studies evaluating different types of therapy for bipolar disorder. The research team reviewed the findings of 55 randomized controlled trials of psychotherapeutic interventions that included a total of 6,010 adult participants with bipolar disorder. The team found moderate-quality evidence that psychological interventions reduced relapses following treatment, and that collaborative care reduced hospital admissions for adults with bipolar disorder. Oud and colleagues found lower-quality evidence that group interventions reduced depression relapses following treatment, and that family psychoeducation reduced symptoms of depression and mania.
The reseachers concluded that there is evidence that therapy can be helpful for people with bipolar disorder. Since some of the evidence was of low quality, more research is needed to identify the most effective therapies for different phases of bipolar disorder.
Editor’s Note: The data are clear that therapy is helpful. In particular, one approach worth emulating is that described in an article by Lars V. Kessing and colleagues in the British Journal of Psychiatry in 2013. They found that comprehensive care in an outpatient mood disorder clinic, which included psychotherapy, psychoeducation, mood monitoring, and drug treatment, reduced relapses significantly compared to treatment as usual.
A recent study confirms that women who are depressed during pregnancy are more likely to experience adverse pregnancy outcomes such as preterm or cesaerean delivery and small or underweight babies. However, antidepressant treatment improved outcomes for pregnant women with depression.
The 2016 study by Kartik K. Venkatesh and colleagues in the journal Obstetrics & Gynecology included 7,267 women who gave birth after at least 20 weeks of pregnancy. About 11% of the women screened positive for depression during their pregnancy. Depressed mothers-to-be were more likely to give birth before 37 weeks and before 32 weeks compared to nondepressed mothers-to-be. The depressed women were also more likely to deliver small babies or babies weighing under 2500g.
About 7% of the women in the study received antidepressant medication. Compared to nondepressed women, the women taking antidepressants did not have greater rates of early delivery or small babies. However, the authors caution that because so few women received antidepressants, the study does not reveal whether antidepressants improve outcomes for depressed pregnant women.
A 2012 study by Geoge I. Papkostas and colleagues found that 15mg/day of the nutritional supplement l-methylfolate calcium (a form of the B vitamin folate that the body can more readily use) improved depression in people who had not responded adequately to treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant. In a follow-up study by Richard C. Shelton and colleagues published in the Journal of Clinical Psychiatry in 2015, the same researchers further analyzed these data and found that l-methylfolate worked better in patients who were overweight (with body mass indexes (BMIs) of 30 or above) and those who had higher than average levels of inflammation at the beginning of the study. Inflammatory markers linked to greater improvement with l-methylfolate included TNF-alpha, IL-8, high sensitivity CRP, and leptin. In overweight participants, higher than average levels of IL-6 were also linked to more improvement on l-methylfolate.
Stimulants are one of the most common medications prescribed to children and adolescents, typically for attention deficit hyperactivity disorder (ADHD). In children of parents with major depression, bipolar disorder, or schizophrenia, stimulant use may come with a risk of psychotic symptoms. A 2016 study by L.E. MacKenzie and colleagues in the journal Pediatrics reported that among children and youth whose parents had one of these psychiatric illnesses, 62.5% of those who had taken stimulants had current psychotic symptoms, compared to only 27.4% of those who had not taken stimulants. The participants with psychotic symptoms tended to have hallucinations that occurred while they were taking stimulants. Doctors may want to consider whether parents have a history of psychiatric illness when deciding whether to prescribe stimulants to children and adolescents with ADHD. Activation is a common side effect of antidepressants in children who have a parent with bipolar disorder. Young people taking stimulants for ADHD should be monitored for psychotic symptoms, particularly if they have a parent with a history of depression, bipolar disorder, or schizophrenia.
The long-acting aripiprazole is administered every 4 to 6 weeks as an injection in the arm or buttocks. The company announced that it would begin releasing the drug immediately. The drug preparation for maintenance treatment is named Maintena while the preparation for acute treatment is named Aristada.