Untreated Episodes of Bipolar Disorder Worsen Over Time, But Prevention is Possible

September 18, 2017 · Posted in Course of Illness · Comment 

Pensive man

A 2017 literature review by researcher Lars V. Kessing and Per K. Andersen in the journal Acta Psychiatrica Scandinavica reports that the greater a patient’s number of previous episodes of bipolar disorder, the more likely that patient is to have a more difficult course of illness and poorer outcomes. The number of episodes was associated with more rapid recurrences, duration and severity of episodes, more automatic episodes (i.e. not triggered by stress), risk of dementia, treatment resistance, lack of recovery between episodes, and brain volume losses.

In an article in the journal Bipolar Disorders in 2016, BNN Editor-in-Chief Robert M. Post described the value of preventive treatment in reducing episodes and protecting the brain from the damage that accompanies them.

Given that episodes, stressors, and bouts of substance abuse can affect the way genes are transcribed via a phenomenon known as epigenetics, preventing these occurrences could lead to an easier course of illness and improved outcomes. Patients should provide their physicians with feedback about their response to prior medications and any side effects they experience over time so that their medication regime can be adjusted until it is maximally effective.

Patients with severe illness and multiple previous episodes may need a complex medication regimen that includes multiple types of medications that target different systems of neurotransmitters.

This philosophy of treatment is presented in several publications, including the 2008 book Treatment of Bipolar Illness: A Casebook for Clinicians and Patients by Post and Gabrielle Leverich, and more recently in the article “Treatment of Bipolar Depression: Evolving Recommendations” in the journal Psychiatric Clinics of North America. An open access article by Post, “New Perspectives on the Course and Treatment of Bipolar Disorders,” published in the journal Edizioni Minerva Medica S.p.A. in 2017, describes the need for early and sometimes complex combination therapy, including the non-intuitive idea that more medications (carefully prescribed) can actually produce fewer side effects than large doses of a single medication.

Another good resource for patients is a daily personal calendar that can be used to track ongoing symptoms, side effects, and response to medications. We offer several types of these calendars free here. My Mood Monitor, or What’s My M3, is a validated screening instrument that can detect depression, anxiety disorders, and mania in response to weekly self-reports. It is available online and as an app, and can be used to track illness course and response to treatment.

Systematic Review Finds Bupropion is Effective for ADHD in Young People

September 14, 2017 · Posted in Potential Treatments · Comment 

Teen takes bupropionA 2016 systematic review by Qin Xiang Ng in the Journal of Child and Adolescent Psychopharmacology found that the antidepressant bupropion (Wellbutrin) can improve attention deficit hyperactivity disorder (ADHD) in children and adolescents.

The review identified 25,455 studies of bupropion for ADHD, but only six included children. All six studies showed that bupropion improved ADHD symptoms in children and adolescents. Head-to-head trials of bupropion and methylphenidate (one of the most common medications to treat ADHD, which most people know by the name Ritalin) found the drugs had similar efficacy rates, although a large double-blind, placebo-controlled multicenter study found that bupropion had a smaller effect size than methylphenidate.

In terms of side effects, methylphenidate was more likely to cause headaches than bupropion, but otherwise the drugs were similar.

Ng suggests that bupropion should be considered for the treatment of ADHD in children and adolescents, but more large trials of the drug are needed. Bupropion may also help children whose ADHD appears alongside conduct, substance abuse, or depressive disorders.

Short Telomeres Associated with Family Risk of Bipolar Disorder

September 13, 2017 · Posted in Genetics, Risk Factors · Comment 

telomeres

Telomeres are bits of genetic material at the end of each strand of DNA that protect chromosomes as they replicate. Short telomeres have been linked to aging and a variety of medical and psychiatric diseases. Stress and depressive episodes can shorten telomeres, while treatment with lithium can lengthen them.

Telomere length is a heritable trait, and a 2017 study by researcher Timothy R. Powell and colleagues suggests that shorter telomeres are a familial risk factor for bipolar disorder.

The study, published in the journal Neuropsychopharmacology, compared the telomere lengths of 63 people with bipolar disorder, 74 of their immediate relatives (49 of whom had no lifetime psychiatric illness, while the other 25 had a different mood disorder), and 80 unrelated people with no psychiatric illness. The well relatives of the people with bipolar disorder had shorter telomeres than the unrelated healthy volunteers.

Relatives (both well and not) and people with bipolar disorder who were not being treated with lithium both had shorter telomeres than people with bipolar disorder who were being treated with lithium.

Another finding was that longer telomeres were linked to greater volume of the left and right hippocampus, and improved verbal memory on a test of delayed recall. This study provides more evidence that taking lithium increases the volume of the hippocampus and has neuroprotective benefits for people with bipolar disorder.

Traumatic Events in Childhood Linked to Shorter Telomeres

September 12, 2017 · Posted in Risk Factors · Comment 

verbal abuse of a child

Telomeres are bits of DNA at the end of chromosomes that protect the DNA as it replicates. Shorter telomeres have been linked to aging and increases in multiple types of medical and psychiatric disorders. A 2016 article in PNAS, the Proceedings of the National Academy of Sciences of the United States of America, reported that cumulative life adversity and particularly stressful or traumatic events in childhood, predict shorter telomere length.

The study by Eli Puterman and colleagues included 4,590 individuals from the US Health and Retirement Study who reported stressful events that had experienced. A single experience of adversity was not linked to short telomeres, but lifetime cumulative adversity predicted 6% greater odds of having shorter telomeres. This result was mainly explained by adversity that occurred in childhood. Each stressful or traumatic event in childhood increased the odds of short telomeres by 11%. These were mostly social or traumatic experiences rather than financial stresses.

Some Antacids Cause Kidney Damage with No Prior Symptoms

September 11, 2017 · Posted in Current Treatments · Comment 

kidneyCommonly used antacids such as Prevacid, Nexium, Prilosec, and Protonix can impair kidney function, according to a 2017 article in the journal Kidney International. These drugs, known as proton pump inhibitors or PPIs, should not be taken long-term without monitoring of kidney function. Other antacids that work by blocking histamine H2 receptors do not interfere with kidney function but may not work as well as PPIs.

Researcher Yan Xie and colleagues found that more than half of people who developed chronic kidney damage while taking PPIs showed no earlier acute signs of kidney dysfunction, meaning there may not be signs of kidney function loss until the damage is irreversible. Xie and colleagues suggest that patients and doctors should be more vigilant about monitoring the use of these medications, since waiting for outward signs of declining kidney function is not a reliable way of detecting damage.

More than 15 million Americans use prescription PPIs to reduce gastric acid, bringing relief to heartburn, ulcers, and acid reflux. Millions more buy PPIs over the counter without consulting a doctor about their use.

The study analyzed Department of Veterans Affairs data from 125,596 new users of PPIs and 18,436 new users of H2 blockers. Acute, reversible symptoms of kidney damage, such as reduction in the urine being cleared from the body, fatigue, and swelling of the legs and ankles were seen in less than 20% of the PPI users. However, more than half of those who developed chronic kidney damage and end-stage renal disease never showed these warning signals beforehand. In contrast, only 7.67% of those taking H2 blockers had chronic kidney disease without acute symptoms, and 1.27% had end-stage renal disease, when kidneys can no longer clear waste from the body, and dialysis or a kidney transplant is required.

Xie and colleagues suggest carefully monitoring kidney function in people taking PPIs, even when there are no outward signs of problems. They also suggest carefully evaluating whether PPIs are necessary, since the risk of kidney damage is serious.

Methylphenidate Does Not Cause Mania When Taken with a Mood Stabilizer

September 8, 2017 · Posted in Comorbidities, Current Treatments · Comment 

ADHDMethylphenidate is an effective treatment for attention-deficit hyperactivity disorder (ADHD). Ritalin may be the most commonly recognized trade name for methylphenidate, but it is also sold under the names Concerta, Daytrana, Methylin, and Aptensio. A 2016 article in the American Journal of Psychiatry reports that methylphenidate can safely be taken by people with bipolar disorder and comorbid ADHD as long as it is paired with mood-stabilizing treatment.

The study was based on data from a Swedish national registry. Researchers led by Alexander Viktorin identified 2,307 adults with bipolar disorder who began taking methylphenidate between 2006 and 2014. Of these, 1,103 were taking mood stabilizers including antipsychotic medications, lithium, or valproate, while 718 were not taking any mood stabilizing medications.

Among those who began taking methylphenidate without mood stabilizers, manic episodes increased over the next six months. In contrast, patients taking mood stabilizers had their risk of mania decrease after beginning treatment with methylphenidate.

Viktorin and colleagues suggest that 20% of patients with bipolar disorder may also have ADHD, so it is not surprising that 8% of patients with bipolar disorder in Sweden receive a methylphenidate prescription.

Mood-stabilizing drugs can worsen attention and concentration, so methylphenidate treatment can be helpful if it can be done without increasing manic episodes. However, Viktorin and colleagues suggest that due to the risk of increasing mania, anyone given a prescription for methylphenidate monotherapy should be carefully screened to rule out bipolar disorder.

The researchers confirmed that taking methylphenidate for ADHD while taking a mood stabilizer for bipolar disorder is a safe combination.

Alterations in Amino Acids in Blood That Affect Metabolism May Help Explain Chronic Fatigue

September 7, 2017 · Posted in Course of Illness · Comment 

exhausted woman

Chronic fatigue syndrome, more recently known as myalgic encephalopathy, is a debilitating and somewhat mysterious illness. However, a 2016 article in the Journal of Clinical Investigation Insight suggests that low blood levels of amino acids related to oxidative metabolism, the process by which oxygen is used to make energy from sugars, may play a role in the illness. High levels of amino acids related to the breakdown of proteins were also seen.

The study by Øystein Fluge and colleagues compared blood concentrations of 20 amino acids in 200 patients with chronic fatigue and 102 healthy participants. There were shortages in 6 amino acids that fuel oxidative metabolism in those with chronic fatigue, particularly women. Men with chronic fatigue had high levels of a different amino acid related to protein catabolism, the breaking down of complex molecules, a process that releases energy.

The differences between men and women with the illness might be because men use muscle tissue as a source for amino acids, while women, who have less muscle mass, use amino acids from blood as fuel.

The changes in both sexes suggest a functional impairment in pyruvate dehydrogenase (PDH), an enzyme that is important for the conversion of carbohydrates into energy. If PDH fails to work and cells turn elsewhere to create energy, muscles may suddenly weaken and lactate may build up, which patients experience as a burning in their muscles after the slightest exertion.

Fluge and colleagues are cancer researchers. They stumbled into chronic fatigue research when they noticed that people with chronic fatigue who were treated for cancer with the drug rituximab saw reductions in their fatigue. Rituximab, which is also used to treat some autoimmune diseases, is a monoclonal antibody directed at B cells. When it binds, it induces cell death. The researchers hope to clarify the link between the immune system and the problems with energy metabolism they have identified in people with chronic fatigue.

Hormone Replacement With Estrogen/Progestogen Combo Increases Breast Cancer Risk More Than Once Thought

September 6, 2017 · Posted in Risk Factors · Comment 

breast exam

A 2016 article in the British Journal of Cancer suggests that previous studies underestimated breast cancer risk in women who received hormone replacement therapy with the combination of estrogen and progestogen. The article by researcher Michael E. Jones and colleagues reported that combined hormone replacement therapy could increase the risk of breast cancer by more than three times, depending on how long a woman is exposed to the therapy. The longer the duration of use, the greater the risk of breast cancer. In the study, women who used other types of hormone replacement therapy, such as estrogen only or tibolone, did not have drastically higher rates of breast cancer than had been reported before.

Jones and colleagues suggest that previous studies did not use long enough follow-up periods to track whether women developed breast cancer while using hormone replacement. Their own study is based on a United Kingdom dataset known as the Breakthrough Generations Study. Study participants completed questionnaires at 2.5 years after recruitment, again at around 6 years, and again around 9.5 years. At the time of recruitment, women using combination hormone replacement therapy had been doing so for a median of 5.5 years.

Women who used combination hormone replacement therapy for 5.4 years were 2.74 times likelier to have breast cancer than those who didn’t receive hormone replacement. Using the combined therapy for more than 15 years increased risk 3.27 times compared to non-users.

The study also reported that as body mass index increased, breast cancer risk increased, regardless of hormone use.

While the study by Jones and colleagues was large (39,183 participants), the number of women who took combined hormone replacement and developed breast cancer was still fairly small (52). Seven of the 52 had taken the combined pill for more than 15 years. One limitation of this study is that these seven women may have skewed the risk assessments somewhat.

Experts suggest that women balance the possible risks and benefits of hormone replacement therapy. The therapy can be helpful in reducing symptoms of menopause, particularly hot flashes.

Using the lowest effective dose for the shortest time possible may be the best option. The increased risk of breast cancer drops after a woman stops using hormone replacement.

Use of Hormonal Contraceptives May Increase Depression Risk in Young Women

September 5, 2017 · Posted in Current Treatments · Comment 

Women, particularly adolescent women, are at increased risk of developing depression if they use hormonal contraceptives, according to a 2016 study in the journal JAMA Psychiatry. The study by Charlotte Wessel Skovlund and colleagues used data from a Danish registry of more than one million women between the ages of 15 and 34 who had no history of depression or other psychiatric disorders. During follow-up (which lasted an average of 6.4 years), 55% of the women were using or had recently used hormonal contraceptives. These women were more likely to be prescribed an antidepressant for the first time, and more likely to be diagnosed with depression compared to women who did not use hormonal contraceptives.

The increased risk of being prescribed an antidepressant varied by contraceptive type. The norgestrolmin patch increased risk by 2.0 times, and the etonogestrel vaginal ring did so by 1.6 times. The levonorgestrel intrauterine device (IUD) made an antidepressant prescription 1.4 times more likely. Progestin-only pills increased risk by 1.34 times and combined oral contraceptive pills increased it by 1.23 times compared to women who did not use oral contraceptives.

The relative risk peaked at around six months after starting hormonal contraceptives.

Patients aged 15–19 were particularly vulnerable to depression. The likelihood of receiving an antidepressant prescription was 1.8 times higher in teens taking combined pills, 2.2 times higher in those taking progestin-only pills, and 3 times higher in teens using hormonal methods of birth control that are not delivered orally compared to those who did not use hormonal contraceptives at all.

Women with History of Depression 20 Times More Likely To Have Postpartum Depression

September 1, 2017 · Posted in Risk Factors · Comment 

mother and infantA study of almost all women who gave birth in Sweden between 1997 and 2008 reports that women with a history of depression are 21.03 times more likely to suffer from postpartum depression than those without such a history. The 2017 article by Michael E. Silverman and colleagues in the journal Depression and Anxiety reports that advanced age and gestational diabetes also increased the likelihood of postpartum depression.

Whether a woman had gone through a depression in the past also affected her other risk factors for postpartum depression. Among women who had been depressed before, having diabetes before pregnancy and having a “mild” pre-term delivery were risk factors for postpartum depression. In contrast, among women with no history of depression, young age, having an instrument-assisted or caesarean delivery, and “moderate” pre-term delivery were risk factors for postpartum depression.

Rates of postpartum depression decreased one month after delivery.

Editor’s Note: About one in five women in the general population experience postpartum depression. All new mothers should be screened for postpartum depression, but especially those with a history of depression. Instituting supportive measures may help prevent an episode.