An Overview of Ketamine for Treatment-Resistant Depression

November 27, 2017 · Posted in Potential Treatments · Comment 

ketamineA 2017 series of articles by researcher Chittaranjan Andrade in the Journal of Clinical Psychiatry reviews the last 10 years of research on ketamine, the anesthetic drug that in smaller doses (0.5 mg/kg of body weight) can bring about rapid antidepressant effects. Ketamine is typically delivered intravenously (though it can also be delivered via inhaler, injected under the skin or into muscles, and least effectively by mouth). Ketamine can improve depression in less than an hour, but its effects usually fade within 3 to 5 days. Repeating infusions every few days can extend ketamine’s efficacy for weeks or months.

Andrade cited a 2016 meta-analysis of nine ketamine studies by T. Kishimoto and colleagues in the journal Psychological Research. The meta-analysis found that compared to placebo, ketamine improved depression beginning 40 minutes after IV administration. Its effects peaked at day 1 and were gone 10–12 days later. Remission rates were better than placebo starting after 80 minutes and lasting 3–5 days.

Several studies have found that ketamine also reduces suicidality.

Andrade reported that both effectiveness and side effects seem to be dose-dependent within a range from 0.1 mg/kg to 0.75 mg/kg.

Side effects of ketamine are typically mild and transient. A 2015 study by Le-Ben Wan and colleagues (also in the Journal of Clinical Psychiatry) that Andrade cited reported that in 205 sessions of ketamine administration, the most common side effects were drowsiness, dizziness, poor coordination, blurred vision, and feelings of strangeness or unreality. The feelings of unreality (dissociative effects) diminish with repeated infusions. Heart and blood pressure may also temporarily increase as a result of ketamine administration.

One study found that ketamine could speed up and add to the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram (Lexapro). A meta-analysis of 10 randomized controlled trials found that ketamine did not improve the effects of electroconvulsive therapy.

Ketamine has some history as a recreational club drug (sometimes known as ‘K’ or ‘special K’), and can be misused or abused.

While there have been many studies of ketamine’s antidepressant effects, Andrade concludes that none is of a standard to justify US Food and Drug Administration approval for the drug. It is hoped that larger, more rigorous trials will be completed in the next few years. However, ketamine is already being used widely to treat treatment-resistant unipolar and bipolar depression.

Vagus Nerve Stimulation Improves Depression When Other Treatments Fail

November 24, 2017 · Posted in Current Treatments · Comment 

VNSVagus nerve stimulation (VNS) has been approved by the US Food and Drug Administration as an adjunctive therapy for treatment-resistant unipolar and bipolar depression since 2005. The treatment consists of a pacemaker-like device implanted under the skin in the chest that delivers regular, mild electrical pulses to the brain via the left vagus nerve.

A 2017 study by Scott T. Aaronson and colleagues in the American Journal of Psychiatry reports that over a 5-year period, people with treatment-resistant depression who received VNS did better than those who received treatment as usual. The 795 participants at 61 US sites had either a depressive episode that had lasted for at least two years or had had three or more depressive episodes and had failed to respond to at least four treatments, including electroconvulsive therapy (ECT). Over five years, those who received VNS had higher response rates (67.6% versus 40.9%) and higher remission rates (43.3% versus 25.7%) compared to those who received treatment as usual.

While the study by Aaronson and colleagues was non-blind and non-randomized, it suggests that VNS could be helpful in the long-term management of treatment-resistant unipolar and bipolar depression.

Editor’s Note: VNS was FDA-approved for treatment-resistant seizures in patients aged 12 and older in 1997 and for children 4 years and older in 2017. It was also approved for cluster headaches in 2017. Insurance coverage and reimbursement for VNS is typically available for these neurological conditions, but not for the treatment of depression. This is an unfortunate example of the stigmatization of psychiatric illness—when an FDA-approved device can be kept from people in need of treatment.

Revising Traumatic Memories in the Reconsolidation Window

October 6, 2017 · Posted in Potential Treatments · Comment 

elderly womanWe have previously described in the BNN how therapies can take advantage of the memory reconsolidation window to reduce the power of traumatic memories. Five minutes to one hour following active emotional recall of a traumatic event, a ‘window’ opens during which therapies can revise or extinguish the traumatic memory. A 2017 article by our Editor-in-Chief Robert M. Post and Robert Kegan in the journal Psychiatric Research describes how the reconsolidation window could theoretically be used to prevent recurring depressive episodes.

The theory is based on the idea that depressive episodes initially stem from stressors, but eventually become ingrained in the brain’s habit memory system. Cognitive behavioral therapy during the memory reconsolidation window might be a good way to disrupt these habit memories.

The memory reconsolidation window has already been used successfully to reduce traumatic memories and even to reduce heroin and cocaine cravings in addiction. The idea in changing traumatic memories, in the words of researcher Göran Högberg in a 2011 article in the journal Psychology Research in Behavior Management, is to “change a reliving intruding memory into a more distant episodic memory.” Post and Kegan suggest that work in depression would have a similar goal, to rework the triggering experience and render the depressive experience “less harsh, severe, [and] self-defeating (guilt-inducing).”
In exploring this new therapeutic approach, Post and Kegan suggest that it might be best to begin with patients whose depressive episodes are triggered by stressors.

The patient would be encouraged to recall the memory of the particular stressor and any emotions related to it. Then they would be prompted to reframe the memory, either by recognizing adaptive aspects of their response, focusing on their youth at the time of the stressor in the case of childhood memories, addressing any guilt the patient may feel, or other techniques used in trauma therapy. Evoking positive feelings during this period via relaxation exercises would be another useful practice.

In addition to targeting stressors that precede depression, the stress of the depressive experience itself could be a target of reframing during the reconsolidation window.
Questions remain, such as whether to target early or more recent memories, and whether this technique would be as useful in reducing manic episodes. Patient characteristics might also affect the success of this type of therapeutic intervention.

Post and Kegan also address how the therapy might be used in different stages of illness, and how it might be combined with other therapies, such as medications or procedures such as repeated transcranial magnetic stimulation (rTMS).

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.

Breathing-Focused Yoga and Meditation Improved Depression

August 24, 2017 · Posted in Potential Treatments · Comment 

woman meditating

A 2016 article in the Journal of Clinical Psychiatry reports that Sudarshan Kriya yoga, a breathing-based meditation intervention, improved depression in people who had had an inadequate response to antidepressants.

In the study by researcher Anup Sharma and colleagues, 25 participants were randomized to either receive the breathing-based meditation training right away or be put on a waitlist to receive the training later. After two months, those who received the intervention showed improvement in depression scores compared to those on the waitlist. The intervention also reduced anxiety.

Vitamin D Deficiency Linked to Depression, But Supplements Helped

August 14, 2017 · Posted in Potential Treatments · Comment 

vitamin DA review article in the Journal of Affective Disorders in 2017 summarized findings linking vitamin D to depression. Researcher Gordon B. Parker and colleagues found an association between low vitamin D levels and depression. They also found that vitamin D supplements improved treatment in people with clinical depression and vitamin D deficiency.

Editor’s Note: Vitamin D supplements are an obvious recommendation for people who are deficient. What has not yet been resolved is whether vitamin D is helpful to people who are depressed but not vitamin D deficient.

In a 2013 study in the Australian and New Zealand Journal of Psychiatry, Nayereh Khoraminya and colleagues suggested that a 1500 IU dose of vitamin D3 combined with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine was more effective than fluoxetine plus placebo in depressed patients who were not necessarily deficient in vitamin D.

Single Dose of Modafinil Improved Memory in People in Remission from Depression

August 3, 2017 · Posted in Potential Treatments · Comment 

memory aidModafinil is a wake-promoting medication used to treat narcolepsy, but studies have also shown that it can improve cognition in people with schizophrenia or attention deficit hyperactivity disorder. It may also help people with lingering cognitive difficulties after recovering from a depression. A 2016 article in the journal Biological Psychiatry reported that a single 200mg dose of modafinil improved performance on tests of episodic memory and working memory (but not planning or attention).

The study by researcher Barbara Sahakian and colleagues included 60 patients who had recently recovered from a depression. They took some cognitive tests to establish a baseline of their performance. A week later, they were given either a placebo or a single dose of modafinil, and two hours later they completed the cognitive tests again. The modafinil group performed better on the memory-related tasks.

While side effects were limited, two participants who received modafinil had sleep disturbances that night.

Longer-term studies are needed to determine whether modafinil is safe and effective if taken over a longer period of time. Cognitive dysfunction can interfere with daily tasks such as work or school and put people at greater risk of relapse, so effective treatments have the potential to greatly improve quality of life for people in remission from depression.

Statins Have Many Benefits

July 25, 2017 · Posted in Current Treatments · Comment 

box of statinsPatients with mood disorders and elevated lipids, cholesterol, or triglycerides can get several benefits by taking statin drugs. Patients with depression are at increased risk for cardiovascular disease, heart attack, and stroke, and statins can lower these risks. Statins lower cholesterol and triglycerides.

Compared to women not taking statins, women taking this class of medications have a lower risk of depression. Men taking statins have a lower incidence of depression following a heart attack than men who are not taking statins.

Several studies over the past two decades have suggested that statins can also decrease the incidence of Alzheimer’s disease, though a 2017 article by Julie M. Zissimopoulos and colleagues in the journal JAMA Neurology suggested the effectiveness of statins in preventing Alzheimer’s may depend on the race and gender of the person taking them. People with depression are at increased risk for Alzheimer’s.

Editor’s Note: Given these many benefits, it may be a good idea for patients with depression or bipolar disorder and high lipid levels to talk to their physician about whether statins would be a helpful treatment for them.

Depression Increases Heart Disease Risk to Same Extent That Obesity, High Cholesterol Do

July 17, 2017 · Posted in Risk Factors · Comment 

heart failureIn men, depression seems to be equal to obesity and high cholesterol in increasing heart disease risk. A German study about heart disease risk included 3,428 men between the ages of 45 and 74 who were observed over a period of 10 years.

In an article in the journal Atherosclerosis, lead researcher Karl-Heinz Ladwig reported that while high blood pressure and smoking are the most powerful risk factors for fatal cardiovascular disease, depression is comparable to obesity and high cholesterol levels. Depression accounts for about 15% of cardiovascular deaths.

Ladwig suggests that depression screening should be standard in patients with other risk factors for heart disease.

Editor’s Note: Long-term preventive treatment for depression may have the added benefit of preventing heart attacks. In people with two prior depressions, most guidelines now recommend lifetime continuation of antidepressant treatment.

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