Repeated Ketamine Reduces PTSD and Depression in the Short Term

September 11, 2018 · Posted in Comorbidities, Potential Treatments · Comment 

iv ketamine

In a 2018 open study by C. Sophia Albott and colleagues in the Journal of Clinical Psychiatry, veterans with post-traumatic stress disorder (PTSD) and a simultaneous diagnosis of major depression were treated with six infusions of intravenous ketamine over a 12-day period (Mondays, Wednesdays, and Fridays for two weeks).

Ketamine produced large improvements in both conditions. The remission rate was 80.0% for PTSD and 93.3% for depression. The median time to first relapse after the treatment was 41 days for PTSD and 20 days for depression.

One side effect of ketamine was that dissociative symptoms increased temporarily with repeated infusions. PTSD symptoms did not worsen among those participants taking ketamine.

The study was intended to evaluate the efficacy, safety, and durability of repeated ketamine infusions. Ketamine has been used in emergency rooms to rapidly treat depression and suicidality, but the effects of a single infusion fade within days.  Albott and colleagues reported that this treatment scenario with multiple ketamine infusions produced rapid results that lasted longer than single ketamine infusions.

Editor’s Note: While this study found that repeated ketamine infusions were safe, it is possible that long-term use may lead to addiction. Researcher Nolan R. Williams and colleagues reported in a 2018 article in the American Journal of Psychiatry that ketamine works via activation of the opiate receptor.  The drug naloxone, which rapidly reverses opiate overdose, completely blocked ketamine’s antidepressant effects.

 

Adipokines May Be the Link Between Mood Disorders and Obesity

January 10, 2018 · Posted in Comorbidities, Resources · Comment 

weightResearchers David J. Bond and Lakshmi Yatham think they may have identified why bipolar disorder and obesity occur so often together. In North America, more than 60% of people with bipolar disorder are overweight or obese, and obesity rates are 60% higher in people with bipolar disorder than in people without bipolar disorder.

Bond and Yatham hypothesized that adipokines might be responsible for both bipolar disorder and obesity. Adipokines are cell signaling proteins that regulate both mood and appetite. Abnormal levels of adipokines in blood could cause both mood episodes and weight gain.

The researchers measured blood levels of five adipokines (leptin, adiponectin, resistin, adipsin, and lipocalin-2) in 53 young people with bipolar disorder. They found three interesting links between adipokines, mood, weight, and medications, which they reported in the Journal of Clinical Psychiatry in 2017.

The first finding was that low levels of leptin and adiponectin (adipokines with antidepressant properties) predicted a greater risk of depressive relapse over a 12-month period. The second finding was that high levels of leptin and adipsin predicted greater weight gain over a 12-month period. The third finding was that treatment with second-generation antipsychotics, which often leads to weight gain and other metabolic side effects, was associated with higher levels of resistin, an adipokine linked to type 2 diabetes.

The findings about leptin were particularly interesting, because leptin’s appetite-regulating effects change with a person’s weight. In the study, low leptin predicted depression, while high leptin predicted weight gain. In people of normal weight, low leptin predicts weight gain, while in overweight or obese people, high leptin predicts weight gain. Bond and Yatham suggest that leptin’s mood-regulating effects may be more consistent, with low leptin increasing depression risk regardless of weight.

These findings may help researchers find ways of treating mood episodes that do not encourage weight gain.

Minimizing Cardiovascular Risk in Bipolar Disorder

January 5, 2018 · Posted in Comorbidities, Risk Factors · Comment 

heartAt the 2017 meeting of the American Association of Child and Adolescent Psychopharmacology, researcher Ben Goldstein gave an overview on cardiovascular risk and bipolar disorder. He noted a study by Nicole Kozloff and colleagues in the Journal of Affective Disorders in 2010 that indicated that onset of cardiovascular disorder occurred an average of 17 years earlier in those with BP I (at age 40-45 years) compared to controls (at age 55-60 years). Several risk factors made onset of cardiovascular disorder more likely, including diabetes, obesity, and the metabolic syndrome (which consists of any three of the five following symptoms: high cholesterol, triglycerides, blood sugar, blood pressure, and waist circumference).

Risk factors include pathophysiological and behavioral mechanisms and certain medications. Pathophysiological mechanisms include inflammation, oxidative stress, and autonomic and endothelial dysfunction.

Behavioral mechanisms include poor diet, exercise, sleep, and increases in tobacco and alcohol use.

Medications could also contribute, with the most to least problematic for weight gain including, among atypical antipsychotics: clozapine, olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and lurasidone. Among mood stabilizers, worst to best for avoiding weight gain are: valproate, lithium, carbamazepine, oxcarbazepine, and lamotrigine.

Goldstein has data from retinal vascular photography (RVP), whereby blood vessels can be observed directly. As opposed to in adults, in youth large vessels are more problematic and arteriolar to venous ratio is abnormally higher in bipolar children compared to normal controls. This ratio is lower in bipolar adults, also reflecting increased cardiovascular risk.
Given the huge loss of life expectancy in bipolar disorder, primarily from cardiovascular disorders, Goldstein urges greater and earlier attention to reducing the pathophysiological, behavioral, and pharmacological mechanisms for poor health. These should be pursued in parallel with attempts at mood stabilization. Read more

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.

Teens with Bipolar Disorder at Increased Risk for Cardiovascular Disease

July 14, 2017 · Posted in Comorbidities, Risk Factors · Comment 

teen blood pressure checkA scientific statement from the American Heart Association reported in 2015 that youth with major depressive disorder and bipolar disorder are at moderate (Tier II level) increased risk for cardiovascular disorders. The combined prevalence of these illnesses in adolescents in the US is approximately 10%.

There are many factors that contribute to this risk, including inflammation, oxidative stress (when the body falls behind neutralizing harmful substances produced during metabolism), dysfunction in the autonomic nerve system, and problems with the endothelium (the inner lining of blood vessels). Lifestyle factors include adversity in early life, sleep disturbance, sedentary lifestyle, poor nutrition, and abuse of tobacco, alcohol, or other substances.

Taking some atypical antipsychotics as treatment for bipolar disorder also contributes to the risk of cardiovascular problems by increasing weight and/or lipid levels. Among the atypicals, ziprasidone (Geodon) and lurasidone (Latuda) come with the lowest likelihood of weight gain.

The statement by Benjamin I. Goldstein and colleagues that appeared in the Heart Association-affiliated journal Circulation suggested that therapeutic interventions should address some of these risk factors to help prevent cardiovascular problems and improve life expectancy for young people with depression or bipolar disorder. These could include a good diet, regular exercise, and treatments with good long-term tolerability that are aimed at preventing episodes.

The Role of Inflammatory Markers and BDNF

Inflammation worsens the risk of cardiovascular problems, while brain-derived neurotrophic factor (BDNF), which protects neurons and plays a role in learning and memory, may improve prospects for someone with depression or bipolar disorder.
A 2017 article by Jessica K. Hatch and colleagues including Goldstein in the Journal of Clinical Psychiatry suggests that inflammation and BDNF are mediators of cardiovascular risk in youth with bipolar disorder. The study looked at 40 adolescents with bipolar disorder and 20 healthy controls.

Those with bipolar disorder had greater waist circumference, body mass index, and pulse pressure than the controls. The youth with bipolar disorder also had higher levels of the inflammatory cytokine Il-6. Participants who had lower BDNF had greater thickness of the carotid vessel internal lining (intima media).

Hatch and colleagues point to the importance of prevention strategies in adolescents with these indicators of increased cardiovascular risk. These data complement the American Heart Association’s recognition of adolescent mood disorders as a large problem that deserves wider attention both in psychiatry and in the media.

Animal Studies Suggest That Oxytocin May Treat Addictions

November 29, 2016 · Posted in Comorbidities, Potential Treatments · Comment 

rat investigating pills

Oxytocin, the hormone that promotes emotional bonding, also regulates a variety of behaviors. Two recent studies suggest that in rats, an injection of oxytocin can prevent drug-seeking behavior.

In the first study, researcher Gary Aston-Jones found that oxytocin reduced the rats’ interest in methamphetamine. The effect was strongest in the rats that started out with the strongest interest in the methamphetamine.

In the second study, researcher Luyi Zhou and colleagues determined that oxytocin also reduced cocaine-seeking behavior in rats. In addition, the oxytocin reversed changes in the brain’s glutamate signaling pathway that were caused by cocaine use.

Both studies, which were presented at the 2016 meeting of the Society of Biological Psychiatry, suggest that oxytocin is a promising potential treatment for drug addictions.

Depression Elevates Stroke Risk

October 18, 2016 · Posted in Comorbidities, Risk Factors · Comment 

depression and stroke risk

Depression has been linked to increases in medical problems such as cardiovascular disease. A new study shows that depression is linked to increased risk of stroke, even when symptoms of depression are in remission.

The 2015 study, by Paola Gilsanz and colleagues in the Journal of the American Heart Association, focused on health and retirement. It included over 16,000 adults aged 50 and up who were interviewed every two years about their health history.

Previous studies have shown a link between depression and stroke risk. Like those studies, the study by Gilsanz and colleagues found that people who were depressed during two consecutive interviews were more than twice as likely to have a stroke in the subsequent two-year period than those who reported few depressive symptoms in the first two visits.

What is new is that in this study, people who were depressed in the first interview but not in the second interview were still at 66% greater risk for a stroke than those with no depression. Those who were depressed only during the second interview not at greater risk for a stroke, implying that depression takes more than two years to affect stroke risk.

Gilsanz and colleagues suggest that they don’t know how depression, remission, and stroke risk interact over the longer term. It is possible that stroke risk diminishes the longer a patient’s depression stays in remission.

It is not clear why depression increases strokes, though some have speculated that depression causes irregular heartbeats. There is not as yet any support for that theory, but high blood pressure, rigid veins, or sticky platelets may be other explanations.

Smoking Ban in New Jersey Jails Drastically Reduced Deaths of Inmates with Mental Illness

October 17, 2016 · Posted in Comorbidities, Risk Factors · Comment 

smoking ban reduces deaths

Policy changes by the New Jersey Department of Corrections drastically reduced the availability of tobacco products in New Jersey jails between 2005 and 2014. Prison commissaries reduced their stock of tobacco, prices increased, sales to minors were banned, and facilities were designated tobacco-free (including for staff and visitors).

Along with this reduction in the availability of tobacco products, the Department of Corrections also introduced smoking cessation programs, began offering nicotine replacement lozenges in commissaries, and increased treatment for tobacco use.

A surprise consequence of the decision to go tobacco-free was a drastic reduction of deaths among prison inmates with mental illness. The mortality rate for these inmates dropped by 48%. In contrast, the mortality rate for inmates without mental illness remained flat before and after the tobacco ban.

People with mental illness are at increased risk of mortality, particularly from cardiovascular illnesses. Now it seems that eliminating tobacco use can go a long way toward improving health and reducing mortality for these people.

Oxytocin Can Block Stress-Induced Relapse of Cocaine Seeking in Animals

February 23, 2015 · Posted in Comorbidities · Comment 

cocaine

Stress can trigger former drug users to begin taking drugs again. In clinical trials, the bonding hormone oxytocin has been found to reduce stress-induced cravings for certain drugs, including alcohol and marijuana. A new study in animals suggests that oxytocin may be able to reduce stress-induced cocaine cravings as well.

Brandon Bentzley and colleagues combined an unpredictable shock to the foot with an alkaloid called yohimbe that comes from a particular tree bark to apply stress to animals who had previously developed a cocaine self-administration habit that had since been extinguished. The combination of the foot shocks and yohimbe brought back robust reinstatement of the animals’ cocaine seeking behaviors, but pretreatment with oxytocin (at doses of 1 mg/kg) prevented this reinstatement.

This research suggests that oxytocin has potential to prevent stress-induced cocaine cravings in people.

Opiate and Alcohol Abuse

January 20, 2015 · Posted in Comorbidities · Comment 

taking pills

Deaths from opiate abuse are occurring in the US at about the same rate as automobile fatalities. At a recent talk, researcher Richard Ries discussed treatment of opiate addictions and the current epidemic of unintended opiate overdoses. Most opiates being abused come from other people’s leftover prescriptions. The best way to prevent opiate abuse is to throw out unused painkillers when they are no longer needed.

Many overdoses from opiates also involve alcohol and benzodiazepines, which can contribute to breathing difficulties.

There are several treatments available that can help patients abstain from using opiates. Treatment with opioid receptor antagonists (such as naltrexone (Rivia or long-acting Vivitrol, which is taken as an injection and lasts for 1 month), partial agonists (like buprenorphine), or full agonists (like methadone) results in, on average, an 80% decrease in the rate of hospitalization and an 80% reduction in crime, as well as a marked decrease in AIDS transmission. Without treatment, it is very difficult for people with opiate addictions to maintain abstinence, and relapse rates are extraordinarily high.

Treatment of Alcohol Abuse and Benzodiazepines

Ries also discussed data on treatment of alcohol abuse. He emphasizes that some aspects of withdrawal, such as sleep disturbance, can last a month or more after a parient’s last drink, putting the patient at high risk for relapse. Gabapentin, which is most often prescribed to prevent seizures, helps patients with this phase. Ries endorsed the combination of gabapentin and naltrexone as especially helpful. Carbamazepine is widely used in Europe for the treatment of alcohol abuse, and Ries also strongly endorsed the drug as another way of avoiding benzodiazepines. Several large placebo-controlled trials suggest that the anticonvulsant topiramate is also effective for long-term alcohol avoidance.

Editor’s Note: Another researcher, Mark Frye, found that women with bipolar disorder are more than seven times more likely than women in the general population to abuse alcohol, often in an attempt to self medicate their residual anxiety and depression. Excellent treatment of mood in bipolar disorder may have the double benefit of helping patients avoid alcohol abuse. The nutritional supplement n-acetylcysteine (NAC) also helps improve mood in bipolar disorder and has positive placebo-controlled data in heroin, cocaine, and alcohol avoidance.

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