Antidepressants Work Better in Major Depressive Disorder than Previously Thought

May 23, 2012 · Posted in Current Treatments, Peer-Reviewed Published Data · Comment 

parent and teens

As we’ve written before, the popular media has sometimes questioned the efficacy of antidepressants for unipolar depression.  A reanalysis of data from previous controlled trials of fluoxetine and venlafaxine that was recently published in the Archives of General Psychiatry provides new evidence that these drugs are significantly more efficacious than placebo in youth, adult, and geriatric populations with major depressive disorder.

The researchers concluded,

To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.

The Risk-Benefit Ratio Encourages the Use of Antidepressants in Unipolar Depression

January 20, 2012 · Posted in Current Treatments · Comment 

antidepressants

Wednesday we reviewed new data that shows that despite the FDA warning that antidepressants can increase suicidal ideation among young people in the first few months they are taken, antidepressants actually reduce acute suicidal ideation and decrease suicidal acts. As we described last year in our article on five myths about antidepressants, antidepressant treatment in recurrent unipolar depression is important to patients’ long-term wellbeing, cognitive functioning, and even life expectancy.

Untreated depression, and particularly untreated recurrent depression, carries high risks not only for lethality by suicide, but also for increases in medical mortality, particularly from cardiovascular disease. In addition to these medical risks, data from many studies suggest that a higher number of prior depressions is associated with increased cognitive dysfunction, and recent large data sets from a case registry in Denmark indicate that patients with four or more prior unipolar or bipolar depressive episodes have double the risk of receiving a diagnosis of dementia in old age. Thus, depressions are dangerous for a patient’s psychological, medical, and cognitive health.

Antidepressants Are Highly Effective in Depression Prevention

In 1992 researcher John Davis completed a meta-analysis of all antidepressant data available at the time in unipolar depression studies and not only found that antidepressant continuation was more effective than placebo in reducing the likelihood of later depressions, but also calculated that the statistical likelihood that this finding was due to chance was minuscule, i.e., p<10-34. John Geddes and colleagues in a meta-analysis in 2003 indicated that there was an approximate 70% reduction in the risk of depressive recurrences with antidepressant continuation compared with discontinuation.

Treatment of a first or second episode of unipolar depression is recommended for six to nine months following achievement of remission. After a third episode, all treatment guidelines of which this editor is aware recommend long-term preventive treatment with antidepressants, particularly if episodes have been severe or close together temporally.  This long-term antidepressant continuation for prophylaxis is much like long-term treatment of high blood pressure or high cholesterol recommended for those with or at high risk for cardiovascular disease.

There is some evidence that cognitive behavior therapy reduces the risk for depressive recurrence in those discontinuing antidepressant treatment, but it appears maximally beneficial to engage both psychotherapeutic and pharmacological treatment to prevent future episodes. Read more

Antidepressants Prevent Suicide in Patients with Unipolar Depression

January 18, 2012 · Posted in Current Treatments, Potential Treatments · Comment 

Researcher A. Kahn reported at the 51st Annual Meeting of the National Institute of Mental Health’s New Clinical Drug Evaluation Unit (NCDEU) in Boca Raton in 2011 that severely depressed and suicidal patients taking citalopram (Celexa) or a combination of citalopram and low dose lithium experienced improvements in depression and suicidal thoughts. This study was unusual because most clinical trials exclude actively suicidal patients. In the group of subjects receiving citalopram plus lithium (300 mg/day and achieving 0.5 mEq/l or higher), there were several indications of better anti-suicide effects than in those on citalopram alone. The authors concluded that with appropriate doses, antidepressants plus lithium may prospectively reduce suicidal thoughts, and that it is possible to conduct clinical trials in severely depressed and suicidal patients if adequate safety measures are included.

Surprisingly, improvement in suicidal ideation preceded improvement in depressed mood per se.

depressed woman

Editor’s note: The study reported here suggests that in those with high suicidal ideation scores at baseline, antidepressants with or without lithium may quickly bring about anti-suicidal effects on thoughts, desires, and behaviors. Whether these effects occur reliably in studies in other groups of patients and in younger individuals remains to be established.

These data are an interesting contrast to data on antidepressant use in those with low levels of suicidality at baseline. A number of studies have suggested that in children and adolescents who were exposed to an antidepressant, a small percentage experienced increases in suicidal ideation in the first two months of treatment compared to patients taking placebo. This led to a Federal Drug Administration (FDA) warning (directed at all patients taking antidepressants) that increases in suicidal ideation and action may occur upon starting antidepressants. 

It is important to note that the warning does not refer to completed suicides; the data set that led to the FDA warning included no completed suicides. More than 70% of those with suicidal ideation do not make an attempt, and the vast majority of attempts do not result in a completed suicide.

Most of the studies that found the slight increase in suicidal ideation in some patients after beginning antidepressant treatment actively excluded acutely suicidal patients. Since the study of citalopram and lithium above used a population of severely depressed and suicidal patients and found that antidepressants improved suicidality, it appears important to consider a patient’s baseline state when considering psychiatric interventions.  In another example, there is an interesting difference between the way depressed patients and non-depressed normal volunteers respond to one night’s sleep deprivation: depressed patients often show dramatic improvement, while normal volunteers tend to feel worse.

More Evidence that Antidepressants Prevent Suicide in Unipolar Depression

A new study by DeLeon published in the Journal of Clinical Psychiatry in 2011 found that during periods of life when unipolar patients were taking antidepressants (compared to times when they were not taking them) the patients experienced 20% fewer suicidal acts or completed suicidesRead more

The Natural Substance Citicoline May Be Useful in Bipolar Disorder with Comorbid Stimulant Abuse

September 6, 2011 · Posted in Comorbidities, Potential Treatments · Comment 

Sherwood Brown and colleagues from the University of Texas Southwestern Medical Center have completed a successful placebo-controlled trial of citicoline for bipolar and unipolar depression with comorbid methamphetamine dependence. Forty-eight participants with methamphetamine dependence and either unipolar or bipolar depression were randomized to either citicoline (2000 mg/day) or placebo for 12 weeks. Those receiving citicoline had significantly greater improvement in scores on the Inventory of Depressive Symptoms compared with those who received placebo, and patients receiving citicoline stayed in the study significantly longer, with completion rates of 41% on citicoline and 15% on placebo.

In 2007, the same team of investigators reported in the Journal of Clinical Psychopharmacology that citicoline had positive effects in bipolar patients with cocaine dependence, who experienced significant decreases in cocaine use and fewer cocaine-positive urine tests while taking citicoline.

Citicoline

Citicoline

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Track Your Moods with Life Charting

January 14, 2011 · Posted in Resources · Comment 

If you have unipolar depression or bipolar disorder and are having trouble stabilizing your mood, we recommend nightly charting of mood, medications and side effects on the easy-to-use Monthly Mood Chart Personal Calendar (pictured below) or the National Institute of Mental Health Life Chart (NIMH-LCM), both of which are available for download.

Sample Mood Chart

Sample Mood Chart

Click on the Life Charts tab above to download the personal calendar, which includes space for rating mood, functioning, hours of sleep, life events, side effects, and other symptoms such as anxiety.  Then bring the chart to each visit with your physician to help in the assessment of treatments.

Life charting can help determine which medications are working partially and need to be augmented further, and which need to be eliminated because of side effects.  Since there are now many potential treatments for depression and bipolar disorder (some FDA-approved and some not), a careful assessment of how well each new treatment works for a particular patient is essential to finding the optimal treatment regimen.

Inflammation and Oxidative Stress in Bipolar Disorder

January 6, 2011 · Posted in Current Treatments, Neurobiology, Potential Treatments · Comment 

A number of studies presented at the 4th Biennial Conference of the International Society for Bipolar Disorders conference in Sao Paulo, Brazil in March reported new data relevant to inflammation and oxidative stress. Both inflammation and oxidative stress increase risk of cardiovascular disorders, and patients with inadequately treated mood disorders lose 10 or more years of life expectancy from cardiovascular disorders compared to the general population. Inflammation and oxidative stress may also contribute to the symptoms, evolution, and progression of the mood disorders themselves.

It is possible that these two processes could become new targets for therapeutic intervention in addition to more traditional psychopharmacological drugs that primarily target the neurotransmitters dopamine, norepinephrine, serotonin, and the neurotrophic factor BDNF. Read more

Thyroid Augmentation Helps Depression (And Bipolar Disorder in Women)

January 4, 2011 · Posted in Current Treatments · Comment 

Low dose thyroid replacement treatment with T3 (Cytomel) (25-37.5 µg) is typically recommended for acute antidepressant augmentation in unipolar and bipolar depression. This approach has few side effects and works even in those with normal thyroid function at baseline.

Thyroid Augmentation

Some data also supports the use of relatively high (supraphysiological) doses of T4 (Synthroid) late in the treatment of highly treatment-resistant patients with unipolar and bipolar disorder.  These supra-physiological doses of T4 typically ranged from 300-500 µg/day, producing a free thyroxine index of 150% of normal. This is usually moderately well tolerated, although minor degrees of sweating, tachycardia (fast heartbeat), and other signs of hyperthyroidism can accompany this regimen. If this approach is employed, it is particularly important to increase the dose of T4 (Synthroid) very slowly because of its relatively long half-life—about 12 days. (That is, if a patient takes a high dose of T4 and then stops their medication completely, 12 days later blood levels will only have decreased to half of what they originally were.)

Findings about high-dose T4 for women with treatment-resistant bipolar illness after the jump. Read more

5 Myths About Unipolar Depression

November 1, 2010 · Posted in Political Commentary · Comment 

Newsweek coverEarly this year, news stories such as Newsweek’s “The Depressing News About Antidepressants” and “Antidepressant Drug Effects and Depression Severity” in the Journal of the American Medical Association (JAMA) created an inadequate picture of the seriousness of clinical depression, and the importance of preventing recurrent episodes with long-term antidepressant treatment. (For a rebuttal, see Psychiatric Times.)

The consequences of this distorted depiction of depression and its treatment are potentially dire for individuals’ health. Some of the popular myths about depression deserve critical review so that patients can make more informed decisions about their own treatment.

Myth 1: Depression is all in your mind
Myth 2: Depression is over-treated
Myth 3: Antidepressant efficacy barely exceeds that of placebo
Myth 4: Antidepressants should be stopped as soon as possible
Myth 5: Depression is a minor medical problem

Myth 1: Depression is all in your mind

This might seem valid, since depression is classified as a mental illness. But depression is not abstract, imaginary, or lacking a solid physical foundation. There is now overwhelming evidence that depression coincides with disturbances in multiple brain and body systems.

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Quetiapine is Effective Across a Spectrum of Illnesses

July 4, 2010 · Posted in Current Treatments · 1 Comment 

The atypical antipsychotic quetiapine (Seroquel or Seroquel XR) has a range of efficacy in a number of illnesses, depending on the size of the dose given.  Read about some of its uses below, including as an adjunct to antidepressants in unipolar depression; as a treatment for generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD); and, at higher doses, as a treatment for mania and depression.  Some of its potential mechanisms of action are described as well.

Chart: Relationship of Receptor Affinity to Dose in Seroquel

Quetiapine's actions on various receptors in the brain (bottom axis) are responsible for its effects in different illnesses

Quetiapine as an adjunct to antidepressants in unipolar depression

Posters at the American Psychiatric Association meeting in San Francisco in May 2009 showed new data from a series of studies of quetiapine in unipolar depression that showed the drug in monotherapy (at 150mg & 300mg) was significantly more effective than placebo. Studies were also positive when quetiapine was used as an adjunct compared with placebo for patients showing inadequate or incomplete responses to antidepressants such as selective serotonin reuptake inhibitors (SSRIs).
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