Using Antidepressants During Pregnancy Likely Does Not Increase Autism Risk

March 14, 2018 · Posted in Current Treatments · Comment 

antidepressants during pregnancy

In the past year or so, several meta-analyses have analyzed data from numerous studies of a possible link between antidepressant use in pregnancy and autism in the offspring. In a 2017 article in the Journal of Clinical Psychiatry, researcher Chittaranjan Andrade offers a meta-analysis of these previous meta-analyses, and determines that while there is a small link between antidepressant use in pregnancy and autism in the offspring, it is most likely the mother’s depressive illness rather than the medications that is responsible for this link.

Andrade found that antidepressant exposure was linked to an increased risk of autism spectrum disorders in the offspring even when the antidepressant use occurred only before conception occurred, when it could not possibly have affected the future fetus’ physiology. This implies that it is the mother’s illness rather than the antidepressant treatment that is a determinant of autism risk.

Depression and Suicidal Thoughts Linked to Brain Inflammation

February 14, 2018 · Posted in Neurobiology · Comment 

depressed man

A 2017 article by Sophie E. Holmes and colleagues in the journal Biological Psychiatry reports that people with major unipolar depression, especially those with suicidal thoughts, have higher levels of the inflammatory marker translocator protein than do healthy individuals.

The participants with depression and suicidal thinking had high levels of translocator protein in the anterior cingulate cortex, which suggests that inflammation is affecting microglia.

Many studies have found links between different indicators of inflammation and mood disorders, leading researchers to speculate whether targeting the immune system could be an effective way to treat mood disorders. Patients with high levels of inflammation often fail to respond to typical treatments for depression.

Some previous research has found evidence of microglial activation in the brains of people who died from suicide.

The small study by Holmes and colleagues used positron-emission tomography, or PET scans, to observe evidence of translocator protein levels in the brain in 14 medication-free participants in a major depressive episode and 13 healthy volunteers. Those with depression, and particularly those with suicidal thoughts, showed more evidence of neuroinflammation.

Combo of Memantine and Sertraline Effective for Unipolar Depression

April 13, 2017 · Posted in Potential Treatments · Comment 

Content young woman lying on couch

A 2016 study in the Journal of Clinical Pharmacy and Therapeutics finds that the combination of memantine (Namenda), a drug used to treat Alzheimer’s disease, and the antidepressant sertraline (Zoloft) improved unipolar depression more than sertraline plus placebo.

The study by Meysam Amidfar and colleagues included 66 patients with moderate to severe unipolar depression. They were divided into two groups—one received sertraline plus memantine for six weeks, while the other received sertraline and a placebo.

The memantine group showed significantly greater improvement at 2 weeks, 4 weeks, and 6 weeks, and significantly greater response at 4 and 6 weeks. There were also more early improvers in the mematine group, and more rapid response to treatment. Both groups improved significantly over the six weeks of treatment.

Larger studies are needed to learn more about the safety and efficacy of memantine combined with sertraline for the treatment of unipolar depression, but this initial study is promising. In 2012, researcher Amit Anand and colleagues reported that in bipolar depression, memantine potentiates the effects of lamotrigine. Memantine also helped rapid cyclers when added to ongoing treatment in an open study of the drug treatment by Athanasios Koukopoulus and colleagues in 2012.

Meta-Analysis Shows Effectiveness of Ketamine for Bipolar and Unipolar Depression

April 22, 2015 · Posted in Potential Treatments · Comment 

ketamine infusion

Ketamine, an anesthetic sometimes used intravenously in the treatment of depression, can bring about rapid onset of antidepressant effects. A new meta-analysis by researcher Michael Bloch and colleagues presented at a recent conference showed that ketamine’s maximum antidepressant effects occur within one day of administration, and its effects remain significant (compared to control conditions) one week following infusion. Ketamine’s effects were diminished in patients taking other medications. There was a trend for better response in patients with bipolar disorder than with unipolar disorder.

Bloch and colleagues analyzed eight earlier studies including a total of 180 participants. In each study, ketamine had been compared to a control condition, either an infusion of saline solution or of midazolam, which mimics ketamine’s sensory effects but does not have antidepressant effects. The researchers are calling for more meta-analyses of ketamine studies to determine which patients respond best to ketamine and how to sustain ketamine’s effects.

Editor’s Note: In another poster presented at the same conference, James Murrough reported that patients with slower processing speed responded best to ketamine. Other findings have shown that those with a history of alcohol abuse and a common genetic variant of brain-derived neurotrophic factor (BDNF), the val-66-val allele of proBDNF, are more likely to respond to ketamine.

Ziprasidone Added to Escitalopram Improved Unipolar Depression

April 17, 2015 · Posted in Potential Treatments · Comment 

unipolar depression

In a new study of patients with major depressive disorder who did not improve after eight weeks of the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram, the addition of the atypical antipsychotic ziprasidone improved their depression more than did placebo. Patients took the combination of escitalopram (20mg/day on average) and ziprasidone twice a day at doses of 20–80 mg.

This was the first randomized, double-blind placebo controlled trial of ziprasidone as an adjunct treatment for unipolar depression. While ziprasidone was more efficacious than placebo, discontinuation of the study due to intolerance was higher among the patients who received ziprasidone.

Editor’s Note: Two atypical antipsychotics (quetiapine and aripiprazole) have been approved by the Federal Drug Administration for augmentation of antidepressants in unipolar depression. Now there have also been placebo-controlled positive trials of two others (ziprasidone and cariprazine).

These findings are of particular interest as the studies of ziprasidone monotherapy in bipolar depression not only failed, but response to ziprasidone and placebo was virtually identical (and negligible).

Brain Activity Differentiates Youth with Bipolar Disorder from Youth with Unipolar Depression

March 24, 2015 · Posted in Brain Imaging, Diagnosis · Comment 

stressed teen girl

Both bipolar disorder and unipolar depression often begin in childhood or adolescence, but it can be difficult to distinguish the two using symptoms only. People with bipolar illness may go a decade without receiving a correct diagnosis. Researcher Jorge Almeida and colleagues recently performed a meta-analysis of previous studies to determine what neural activity is typical of children with bipolar disorder versus children with unipolar depression while processing images of facial emotion. They found that youth with bipolar disorder were more likely to show limbic hyperactivity and cortical hypoactivity during emotional face processing than youth with unipolar depression. Almeida and colleagues hope that this type of data may eventually be used to diagnose these disorders or to measure whether treatment has been successful.

Transcranial Direct Current Stimulation Plus Zoloft Has Better Antidepressant Effects Than Either Treatment Alone

January 29, 2014 · Posted in Potential Treatments · Comment 

transcranial direct-current stimulationTranscranial direct current stimulation (tDCS), in which a barely perceptible level of electrical current is applied directly from one side of a patient’s scalp to the other, is a promising treatment for patients with tought-to-treat depression. A 2013 study by Brunoni et al. in JAMA Psychiatry examined whether combined treatment using tDCS and the selective-serotonin reuptake inhibitor (SSRI) antidepressant sertraline (Zoloft) would be a safe and effective treatment for unipolar depression. The combination was better than either treatment alone and better than placebo.

The six-week study used what is called a 2×2 factorial design, in which 120 patients with unipolar depression received either 50 mg/day of sertraline or placebo and also received either real tDCS or a sham procedure. The tDCS was administered in twelve 30-minute sessions, one per day Monday through Friday during the first two weeks, followed by one every other week. TDCS consists of an anodal (positive) and cathodal (negative) current placed at particular positions on the head. This study used 2 microamps of anodal left/cathodal right prefrontal stimulation for the tDCS treatment.

While the combination of sertraline and tDCS was significantly better than all three other treatment options (sertraline plus sham procedure, placebo plus tDCS, and placebo plus sham procedure), sertraline by itself and tDCS by itself resulted in similar efficacies. However, TDCS by itself was also significantly better than placebo, while sertraline by itself was not.

Side effects among the different treatment options were similar, except those who received tDCS had more scalp redness. There were seven instances of patients developing mania or hypomania during the study, five of which occurred in the combined tDCS and sertraline treatment group, higher than the 1–2% rate that would be expected in a study of unipolar depression.

Buspirone and Melatonin Together May Treat Unipolar Depression

January 16, 2014 · Posted in Potential Treatments · Comment 

smiling woman

The combination of the anti-anxiety drug buspirone (trade name Buspar) and melatonin, a hormone that regulates cycles of sleep and waking, may be effective for depression. Researcher Maurizio Fava and other researchers at Massachusetts General Hospital report that low-dose buspirone (e.g. 15 mg/day) combined with a 3 mg dose of melatonin produced significant antidepressant effects in a six-week study of patients with unipolar depression.

While buspirone is not a potent antidepressant at low doses, the combination of buspirone and melatonin exerted significant effects, leading to better antidepressant response than did either placebo or 15 mg of buspirone alone. Another benefit of the combination is that the low dose of buspirone minimizes side effects.

Buspirone is a serotonin 5HT1A receptor partial agonist, meaning that it produces weak activity at this serotonin receptor, but does not allow it to get overstimulated.

Cognitive Behavioral Therapy Tailored For Children and Adolescents

December 5, 2013 · Posted in Current Treatments · Comment 

Teen with therapist

At a symposium on early-onset depression at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, Betsy Kennard described a course of cognitive behavioral therapy tailored to eliminating residual symptoms in children with unipolar depression who had no family history of a parent with bipolar disorder. In the same study Graham Emslie discussed, the investigators considered cognitive behavioral therapy for the treatment of childhood- and adolescent-onset depression.

The therapy was aimed at achieving health and wellbeing and focusing on positive attributes and strengths in the child, and it was designed to be a shorter than usual course (i.e. four weekly sessions, then four every other week, and one at three months). This regimen typically also included three to five family sessions. Other key components of the therapy included anticipating and dealing with stressors, setting goals, and practicing all the skills learned.

On a visual timeline, children identified and wrote down past stressors, how they felt when depressed, their automatic cognitions, ways they would know when they were feeling down again (i.e. feeling isolated, angry at parents, etc.), their strengths and skills, what obstacles to feeling better existed and how to circumvent them, and their long-term goals.

The therapy was based on the research of Martin Seligman and Giovanni A. Fava, plus Rye’s Six S’s (soothing, self-healing, social, success, spiritual, and self-acceptance). The children participated in practice and skill-building in each domain. Sleep hygiene and exercise were emphasized. The idea of “making it stick” was made concrete with phrases on sticky notes taken home and put up on a mirror. Postcards were even sent between sessions as reminders and for encouragement.

Editor’s Note: Most depressed kids don’t get completely well (only about 20% after an acute course of medication). Something must be added. This kind of specialized cognitive behavior therapy works and keeps patients from relapsing. This study included only those children with unipolar depression whose parents did not have bipolar disorder. However, Emslie noted that depressed children of a bipolar parent also had an exceedingly low rate of switching into mania (2 to 4%) in his experience, so fluoxetine followed by cognitive behavioral therapy might be considered for treating unipolar depressed children of a bipolar parent.

Once children have developed bipolar disorder, evidenced by hypomania or mania followed by depression, antidepressants are to be avoided in favor of mood stabilizers and atypical antipsychotics, since there is a higher switch rate in these youth when they are prescribed antidepressant monotherapy.

Since children with bipolar disorder are at such high risk for continued symptoms and relapses, the strategy of adding cognitive behavioral therapy to their successful drug treatment would appear appropriate for them as well as those with unipolar depression, especially since there is a large positive literature on the efficacy of cognitive behavioral therapy, psychoeducation, and Family Focused Therapy (FFT) in children and adults with bipolar depression. As noted previously, FFT is very effective for children at high risk because of a parent with bipolar disorder and who are already symptomatic with anxiety, depression or BP-NOS.

Moral of the story: getting kids with unipolar or bipolar depression well and keeping them well is a difficult endeavor that requires specialized, combined medication and therapy approaches and follow-up education and therapy. This is for sure. The hope would also be that good early and long-term intervention would yield a more benign course of recurrent unipolar or bipolar disorder than would treatment as usual (which all too often consists of medication only).

Irritability and Unipolar Depression in Kids

February 15, 2013 · Posted in Diagnosis, Risk Factors · Comment 

irritable girlAt the 2012 Pediatric Bipolar conference sponsored by the Ryan Licht Sang Foundation, Graham J. Emslie gave a talk on irritable mood and unipolar depression in youth.

Irritability is common in unipolar depression. Emslie suggested that if a child’s irritability is severe and the child destroys objects and denies being irritable, bipolar disorder might be likely. Irritable unipolar depressed children will generally acknowledge being irritable.

Emslie reported that 96% of youth in his randomized placebo-controlled studies of selective serotonin reuptake inhibitor antidepressants (SSRIs) recovered from their unipolar depression, but 46.6% relapsed. Those children with residual depressive symptoms were at double the risk for relapse into a depression compared to those who remitted completely. In those without residual depressive symptoms, there were no relapses if the children stayed on their medications.

Children were excluded from Emslie’s study if they had a positive family history of bipolar disorder, and perhaps because of this, very few participants switched into mania with antidepressants.

MORAL:  Treat to remission and stay on the antidepressants associated with the remission. This has previously been found to be important for adults as well. (Emslie added that he would advise that a child stay on an antidepressant for at least a year after a remission was achieved, and longer if the child had difficulties in academic performance or relationships at school.)

Children with unipolar major depression who had a few manic symptoms at a subsyndromal level had poorer outcomes in Emslie’s study. The presence of subsyndromal manic symptoms in bipolar depressed adults is a risk factor for increased switching into mania when antidepressants are added to a mood stabilizer.

Comorbid substance abuse is another risk factor for poor outcome in childhood depression.

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