Management of Unipolar and Bipolar Depression During Pregnancy

March 5, 2018 · Posted in Current Treatments, Potential Treatments · Comment 

pregnancyAt the Maryland Psychiatric Research Society’s continuing medical education conference in November, Lauren Osbourne, Assistant Director of the Women’s Mood Disorders Clinic at Johns Hopkins Hospital, gave a presentation on the management of mood and anxiety during pregnancy and lactation. She had a number of important ideas for physicians and patients to consider in their decision-making process.

According to Osbourne, 60%-70% of pregnant women with unipolar depression who discontinue their antidepressants relapse. Of those with bipolar disorder who discontinue their mood stabilizers, 85% relapse, while 37% of those who stay on their medications relapse.

Something to consider when deciding whether to continue medication while pregnant is that depression in pregnancy carries its own risks for the fetus. These include preterm delivery, low birth weight, poor muscle tone, hypoactivity, increased cortisol, poor reflexes, and increased incidence of attention deficit hyperactivity disorder (ADHD) and other behavioral disorders.

The placenta makes an enzyme 11-BHSD2 that lowers the stress hormone cortisol in the baby. However, this enzyme is less active in depression, exposing the fetus to higher levels of cortisol.

Thus, the decision about whether to continue medications during pregnancy should consider the risks to the fetus of both the mother’s depression and the mother’s medications.

Most antidepressants are now considered safe during pregnancy. There have been reports of potential problems, but these data are often confounded by the fact that women with more severe depression are more likely to require antidepressants, along with other risk variables such as smoking or late delivery (after 42 weeks). When these are accounted for by using matched controls, the apparent risks of certain antidepressants are no longer significant. This includes no increased risk of persistent pulmonary hypertension, autism, or cardiac malformations.

There may be a possible increased risk of Neonatal Adaption Syndrome (NAS) in the first weeks of life in babies who were exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants in the third trimester. This syndrome presumably results from antidepressant withdrawal, and can include respiratory distress, temperature changes, decreased feeding, jitteriness/irritability, floppiness or rigidity, hypoglycemia, and jaundice. There is not yet a robust literature on the syndrome, but Osbourne suggested that it disappears within 2 weeks of birth.

In her practice, Osbourne prefers to prescribe sertraline, which has the best safety data, along with fluoxetine. Sertraline is also OK for breastfeeding. There is less data on bupropion, but it also appears to be safe during pregnancy. Endocrine and enzyme changes in pregnancy typically cause a 40% to 50% decrease in concentrations of antidepressants, so doses of antidepressants typically must be increased in order to maintain their effectiveness.

Osbourne ranked mood stabilizers for bipolar disorder, from safest to most worrisome. Lamotrigine is safest. There is no evidence linking it to birth defects, but higher doses are required because of increased clearance during pregnancy. Lithium is next safest. There are cardiac risks for one in 1,200 patients, but these can be monitored. Carbamazepine is third safest. One percent of babies exposed to carbamazepine will develop spina bifida or craniofacial abnormalities. Valproate is least safe during pregnancy. Seven to ten percent of babies exposed to valproate will develop neural tube defects, other malformations, or developmental delay, with a mean decrease of 9 IQ points. The atypical antipsychotics all appear safe so far.

Alternatives and Adjuncts to Medications in Pregnancy

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Continuing Lithium Treatment Does Not Increase Kidney Failure

February 26, 2018 · Posted in Current Treatments · Comment 

kidneyA risk of long-term lithium treatment is that it can cause kidney damage. However, a new study suggests that continuing lithium treatment after a diagnosis of chronic kidney disease does not necessarily increase the risk of irreversible end-stage kidney disease, which is defined as either the need for either chronic dialysis or a kidney transplant.

The 2017 study by researcher Lars Kessing and colleagues in the journal Acta Psychiatrica Scandinavica used Danish health databases to track data from all individuals who received a diagnosis of chronic kidney disease between 1995 and 2012 and also had a history of lithium treatment (754 patients) or anticonvulsant treatment (5,004 patients). Kessing and colleagues found that patients who continued taking lithium after an initial diagnosis of chronic kidney disease had decreased rates of end-stage kidney disease. This also held true for those who continued anticonvulsant treatment after a diagnosis of kidney disease.

One point of uncertainty was introduced by the finding that the subset of participants who were taking lithium specifically to treat bipolar disorder did have a higher rate of end-stage kidney disease. This was not true of the participants who were taking anticonvulsants to treat bipolar disorder.

Kessing and colleagues concluded that after an initial diagnosis of chronic kidney disease, continuing lithium did not necessarily increase end-stage kidney disease. Switching to an anticonvulsant, as is sometimes the practice after a kidney disease diagnosis, may not confer any benefit.

Lithium Treatment Lowers Suicide Rate in People with Bipolar Disorder

February 23, 2018 · Posted in Current Treatments · Comment 

lithium

A large study that made use of a Swedish health database has shown that lithium reduces suicide rates in bipolar disorder. The study by researcher Jie Song and colleagues was published in the American Journal of Psychiatry in 2017.

The study included eight years of data from 51,535 people with bipolar disorder. During that time, there were 10,648 suicide-related events recorded, such as suicide attempts or completed suicides. The researchers compared suicide rates when patients were taking lithium to rates when they were off the drug, and found that lithium reduced attempted or completed suicide by 14%. Song and colleagues also looked at suicide rates for people taking valproate, and found that these were no better than when patients were off valproate, implying that treatment alone is not enough to reduce the suicide rate and the benefit is specific to lithium use.

Song and colleagues estimate that 12% of the suicide-related events among the patients included in the study might have been avoided if the patients had taken lithium for the entire study period. While there are other clinical considerations to make when selecting an appropriate treatment for a given patient, the researchers suggest that lithium treatment should be considered for patients with bipolar disorder who have expressed suicidal intentions or who are otherwise at risk for suicide.

Gabapentin May Increase Opioid-Related Deaths

February 2, 2018 · Posted in Current Treatments, Risk Factors · Comment 

topiramateThe anticonvulsant gabapentin is sometimes prescribed for chronic pain conditions along with opioids. A 2017 article by researcher Tara Gomes in the journal PLOS Medicine reports that compared to opioid prescriptions alone, co-prescription of gabapentin increases the risk of an opioid-related death by 49%. The risk was increased by 60% for those receiving moderate or high doses of gabapentin (those above 900 mg/day).

The increased risk when the drugs are taken together may be because both gabapentin and opioids depress the respiratory system. Opioids also slow the gastrointestinal system, meaning that more gabapentin is absorbed by the intestines than occurs when gabapentin is prescribed alone.

Gomes and colleagues looked at cases of patients who were prescribed opioids and had opioid-related deaths, and matched these with similar patients who had not died while taking prescription opioids during the same time period. The researchers found that having taken gabapentin in the previous 120 days dramatically increased the risk of death from opioid-related causes.

Gomes and colleagues suggest that caution should be used when prescribing gabapentin and opioid drugs at the same time.

Omega-3 Fatty Acids Improve Executive Function in Youth with Mood Disorders

January 29, 2018 · Posted in Current Treatments · Comment 

omega-3 fatty acids

A 2017 study by Anthony T. Vesco and colleagues in The Journal of Child Psychology and Psychiatry suggests that in youth with depression or bipolar not otherwise specified (BP-NOS), omega-3 fatty acid supplements improve executive functioning and behavior regulation compared to placebo.

Ninety-five participants aged 7–14 years received two capsules daily of either omega-3 fatty acids (1.87g total per day, mostly consisting of EPA) or placebo for 12 weeks. Those who received omega-3s showed improvement in executive functioning (which can include planning and decision-making), behavioral regulation, and metacognition, as rated by their parents.

Editor’s Note: Since omega-3 fatty acids have no known side effects, there is little reason not to try them in youth with depression or bipolar disorder.

Omega-3 Fatty Acids Improve ADHD

January 26, 2018 · Posted in Current Treatments · Comment 

sources of omega-3 fatty acidsA 2017 systematic review and meta-analysis found that omega-3 fatty acid supplementation improves symptoms of attention-deficit hyperactivity disorder (ADHD) in children and adolescents. The article by Jane Pei-Chen Chang and colleagues in the journal Neuropsychopharmacology identified seven randomized controlled trials in which omega-3 fatty acids improved clinical symptoms of ADHD, and three trials in which omega-3s improved cognitive measures associated with attention.

The meta-analysis also found that children and adolescents with ADHD have lower than normal levels of the omega-3s DHA and EPA, in addition to lower total levels of omega-3s measured in blood and cheek tissues.

Chang and colleagues suggest that omega-3 fatty acid supplementation is a potentially helpful and largely risk-free treatment option for ADHD in children and adolescents.

Eye Movement Desensitization and Reprocessing Can Improve PTSD

January 18, 2018 · Posted in Current Treatments · Comment 

A 2014 meta-analysis of clinical trials showed that the therapeutic technique known as eye movement desensitization and reprocessing (EMDR) can reduce symptoms of post-traumatic stress disorder (PTSD). The meta-analysis also established that longer durations of EMDR treatment correlated with better outcomes.

The meta-analysis by Ying-Ren Chen and colleagues in the journal PLOS One evaluated 26 randomized controlled trials of EMDR in people with PTSD. Chen and colleagues found that EMDR reduced PTSD symptoms, depression, anxiety, and subjective distress.

EMDR is a psychotherapeutic technique intended to reduce the distress that a patient feels about a traumatic memory. The patient is encouraged to recall the traumatic event while focusing on an external stimulus. Typically this would mean using their eyes to track the therapist’s hand moving back and forth from left to right. This process can help patients reprocess the trauma and alleviate the stress that they feel upon recalling the traumatic memory.

Chen and colleagues found that EMDR sessions that lasted longer than one hour were more effective than those that lasted less than an hour. Another finding that was that groups led by therapists who were experienced in PTSD group therapy were more effective than groups led by therapists without that experience.

Other more recent research has established that traumatic memories can be reprocessed or even extinguished by making use of the memory reconsolidation window. Five minutes to one hour after a patient engages in active emotional recall of a traumatic memory, a window of time opens in which that memory is subject to reinterpretation and revision.

An experienced therapist can create a safe environment for a patient to recall traumatic events and find alternative ways of interpreting the experience—for example, by focusing on their strength in surviving the experience. This process resembles EMDR in many ways, but without the eye movements.

In a 2017 article in the journal Psychiatry Research, BNN Editor-in-Chief Robert M. Post and colleague Robert Kegan discuss the possibility of using the reconsolidation window to reprocess stressors that led to a depressive episode.

Proton Pump Inhibitors Linked to Gastric Cancer

January 16, 2018 · Posted in Current Treatments · Comment 

helicobacter pylori in the stomachProton pump inhibitors (PPIs), a type of medication used to reduce gastric acid, have been linked to gastric cancer in a new study by Ka Shing Cheung and colleagues. A 2017 article in Gut, the journal of the British Society of Gastroenterology, reports that receiving PPIs to treat stomach infections from the bacterium Helicobacter pylori increases the risk of later gastric cancer.

The study relied on a territory-wide health database in Hong Kong. Out of 63,397 subjects, 153 developed gastric cancer after being treated for Helicobacter pylori. PPI treatment was associated with a 2.4-fold increase in risk of gastric cancer, while treatment with histamine-2 receptor agonist drugs did not increase cancer risk.

Editor’s Note: PPIs are widely used in psychiatric patients. Care should be taken with their long-term use.

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.

FDA Approves New Higher Dose of Valbenazine for Tardive Dyskinesia

December 15, 2017 · Posted in Current Treatments · Comment 

tardive dyskinesia

The US Food and Drug Administration has approved an 80 mg capsule dose of valbenazine (Ingrezza) for tardive dyskinesia (jerky, involuntary movements of the face, especially the mouth and tongue, fingers and body that can be a side effect of antipsychotic medication). Valbenazine, a selective vesicular monoamine transporter 2 inhibitor, was the first drug FDA-approved for tardive dyskinesia. The FDA initially approved a dosage of 40 mg/day in April 2017. The 80 mg/day dose was approved in October 2017.

The new approval was based on a 6-week clinical trial in which 80 mg of valbenazine improved tardive dyskinesia significantly compared to placebo. Improvement continued over 48 weeks of treatment.

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