Thyroid hormone and Depression

This is a brief note about the use of T3 (the active from of thyroid hormone in the body) in the treatment of depression. Thyroid augmentation, though usually well tolerated, has the potential for serious side effects and should only be done in conjunction with a professional licensed to prescribe it.

Low levels of thyroid hormone are associated with depression, and many clinicians check a TSH level (a very sensitive screening test for low thyroid, known as hypothyroidism) as part of the assessment of symptoms of depression.

It is less widely known that even if a person has normal levels of thyroid, they may benefit from taking T3 as a supplement or augmentation agent along with their antidepressant.

T3 has primarily been studied in combination with tricyclic antidepressants (such as imipramine, doxepin and nortriptyline). However, it has also been combined with an SSRI (selective serotonin reuptake inhibitor), such as in the STAR-D studies. In one of the STAR-D studies, when citalopram (a SSRI) was ineffective on it’s own for major depression, either T3 or Lithium was added to citalopram. T3 and lithium were equally effective as an add-on agent for decreasing symptoms of depression; however, T3 was better tolerated.

In general it appears to be more helpful for women than men, and very well tolerated. In my experience it works quickly, but in the STAR-D study the mean time to becoming well took 6 weeks, and for some this did not occur until week 14. So be patient with it.

The usual starting dose is 25 micrograms (not milligrams, the typical unit of dosing in psychiatry), though sometimes it is better to start with just 12.5 mcg. This dose is usually continued for about 2 weeks before assessing benefits and side effects. The maximum dose is 50 mcg/d. Don’t be surprised if you find that it helps and you start wondering if an even higher dose would work better. Don’t increase it on your own. After a month a TSH level should be checked to make sure that you are not getting too much T3.

T3 is generally quite safe and easy to tolerate, but too much is associated with atrial fibrillation and osteoporosis. Symptoms of hyperthyroidism, a condition in which the body is making too much thyroid hormone (or is taking too much) include sweating, loose stools, anxiety, rapid heart rate and heat intolerance.

T should be taken on an empty stomach to improve absorption. Antacids, zinc and iron supplements can decrease absorption.

I have frequently discussed using T3 as an augmentation agent. Both I and my patients have been struck by it’s lack of side effects and the improvement in energy and mood that they experienced. One of it’s most attractive features as an add-on agent is it’s ability to improve energy, and for some people, to decrease appetite, or at least not increase appetite (which is a side effect of many augmentation agents). It has sometimes been hard to put the brakes on over enthusiastic patients who have suffered from depression, decreased motivation, lack of enthusiasm and no pleasure for a long time. It is easy to understand the reasoning: “if 50mcgs helps, 75 or a 100 would be fantastic”. Don’t do it. Check a TSH level, and respect that though T3 can help, it is a potent substance and must be used appropriately.

For more information refer to the following articles:

1. Augmenting antidepressants with triiodothyronine: An underutilized strategy:T3 augmentation can improve depressive symptoms in patients without subclinical hypothyroidism

Current Psychiatry Vol. 10, No. 07 / July 2011 Daniel Gih, MD

2. T3 Augmentation in Major Depressive Disorder: Safety Considerations

Lisa J. Rosenthal, M.D., Whitney S. Goldner, M.D., John P. O’Reardon, M.D.



Omega-3 Fatty Acids and Depression

Bottom line: Taking 1-4 grams per day of O3FA can decrease symptoms of depression, when the EPA component of the supplement is at least 60% of the total fatty acid content. DHA, another omega-3, should not be used by itself or make up more than 40% of the total fatty acid content.

Background: Many studies have been published looking at the usefulness of omega-3 fatty acids in the treatment of depression, bipolar disorder, schizophrenia and other conditions. The results have been conflicting and confusing. Recent articles in the Journal of Clinical Psychiatry (Dec. 2011) and Current Psychiatry (Sept. 2012) help to make sense of the data. Meta-analyses of fatty acid studies in the treatment of depression have found that when used alone the omega-3 fatty acids are not effective in decreasing depressive symptoms. DHA, one of the major omega-3’s, is not helpful for depression. EPA, another omega-3, is effective. However, the benefit from from EPA is most apparent when

* the depression is on the severe end of the spectrum

* the patient is on antidepressant treatment (the fatty acid is not used alone)

* EPA makes up at least 60% of the fatty acid content of the supplement

The amount of omega-3 that works best has not been determined. It is recommended that at least 1 gram be taken each day, with a maximum dose of perhaps 4 grams. Higher doses have been associated with less benefit.

Example: If you are taking an antidepressant, say sertraline 150 mg/d or venlafaxine 225 mg/d, and you are still suffering from significant symptoms of depression, and do not want to increase the dose (a reasonable option in both cases), adding 1-2 grams/d of omega-3 fatty acid (with EPA at least 60% of the total) made by a reputable company may be a good choice. There is no evidence whether it is more or less likely to help continuing symptoms of depression than any of the many other options, at least so far. Side effects are pretty minimal, unless you get the fishy tasting burps. Also, the omega-3s are not recommended for someone with a bleeding disorder. Eating fish 2-3 times a week(at least those high in omega-3s, such as salmon, sardines, herring and halibut) will get you plenty of omega-3.

1) Morreale, M Omega-3 Fatty Acids for psychiatric Illness. Current Psychiatry Vol. 11, No. 09 / September 2012

2) Sublette,M et al Meta-Analysis of the Effects of EPS in Clinical Trials of Depression. Journal of Clinical Psychiatry2012;72(12):1577

Group Psychoeducation for Bipolar Disorder

Medication is only 1 way to decrease the likelihood of  having another episode for people with bipolar disorder. In a study of 120 patients with bipolar disorder who were currently euthymic (back to baseline), the addition of group psychoeducation significantly reduced the chances of having another episode compared to participating in a support group.

The psycho-education group emphasized

1) early detection of symptoms of an impending mood episode

2) sticking with treatment (such as taking medication regularly, attending appointments, etc.)

3) lifestyle regularity (having a routine or schedule for physical activity, bedtime, social activity)

Though more people in the support group completed the study, those in the psycho-education group

1) fewer mood episodes

2) fewer days hospitalized

3) a longer time to the next episode

Though this is not a new study, being published 10 years ago, subsequent studies have backed up it’s central finding: there are ways to decrease the chances of having another episode in bipolar disorder in addition to taking medication.

The take away message is that learning about bipolar disorder, sticking with the treatment plan and leading a regular lifestyle can help to stay better.

A Randomized Trial on the Efficacy of Group Psychoeducation in the Prophylaxis of Recurrences in Bipolar Patients Whose Disease Is in Remission 

Francesco Colom, PhD; et. al.
Arch Gen Psychiatry. 2003;60(4):402-407. doi:10.1001/archpsyc.60.4.402.

Folate and Depression

Folate, which is involved in making neurotransmitters such as serotonin and dopamine, has been found to be low in some individuals with depression. And low levels appear to be associated with a decreased response to antidepressants.

In an article from the December, 2012 issue of the American Journal of Psychiatry, Papakostas and colleagues found that L-methylfolate (folate is converted into L-methylfolate prior to it’s role in making neurotransmitters) increased the number of responders when it was added to an SSRI-type antidepressant. These patients had been taking an SSRI (a category which includes fluoxetine, sertraline, citalopram, paroxetine and others) for 8 weeks without responding to the SSRI alone. 32% responded to L-methylfolate plus SSRI, versus 14% taking placebo and SSRI.

The number needed to treat (NNT, one of the better measures of the practical usefulness of a treatment) was 6, which means it is a clinically useful strategy.

l-Methylfolate was well tolerated when added to an SSRI, with rates of side effects no different from those reported with placebo plu an SSRI.

An important unanswered question is whether it is necessary to use L-methylfolate (marketed as Deplin at about $90-$95 dollars a month), or if over the counter, very inexpensive, folic acid would be just as effective. Another question is what dose of folic acid should be used if added as an augmentation agent in the treatment of depression.

l-Methylfolate as Adjunctive Therapy for SSRI-Resistant Major Depression: Results of Two Randomized, Double-Blind, Parallel-Sequential Trials

George I. Papakostas, M.D., et. al.

The Evolving Story of Folate in Depression and the Therapeutic Potential of l-Methylfolate

J. Craig Nelson, M.D.

Creatine and Depression

In an article published in the American J of Psychiatry in 2012, the addition of creatine to escitalopram (an SSRI, marketed under the brand name Lexapro) led to a more rapid decrease in symptoms and a greater remission rate (the most important outcome parameter when assessing a treatment for depression) in women with major depression. Escitalopram was given at 10mg/d for 1 week, then 20mg/d. Creatine was given at 3 grams a day for 1 week, then 5 grams a day. There was no difference between placebo and creatine in the type of side effects experienced. No serious side effects occurred. Side effects reported included tension headaches, nausea, vomiting and sleep difficulties.

The number needed to treat (NNT) for remission, one of the best measures of the practical usefulness of a treatment, was 4. 52% of patients taking creating with escitalopram went into remission, versus 25% of those taking placebo plus escitalopram.

A Randomized, Double-Blind Placebo-Controlled Trial of Oral Creatine Monohydrate Augmentation for Enhanced Response to a Selective Serotonin Reuptake Inhibitor in Women With Major Depressive Disorder

In Kyoon Lyoo, M.D., Ph.D., Sujung Yoon, M.D., Ph.D., Tae-Suk Kim, M.D., Ph.D., Jaeuk Hwang, M.D., Ph.D., Jieun E. Kim, M.D., Ph.D., Wangyoun Won, M.D., Sujin Bae, Ph.D., Perry F. Renshaw, M.D., Ph.D.

American Journal of Psychiatry, Sep 2012; 169 (9); 937-945. doi: 10.1176/appi.ajp.2012.12010009

PTSD: Overview

Much of the following is based on a lecture by Bruce P. Capehart, M.D. given on 5/10/2012, as part of the Massachusetts General Hospital Psychiatric Academy series From the War Zone to the Home Front: Supporting the Mental Health of Veterans and Their Families.

What helps in the treatment of PTSD

1) Evidence Based Psychotherapy (Cognitive Behavioral, EMDR, Cognitive Processing Therapy)

2) The right medication

3) Treating insomnia

4) Avoiding alcohol and drugs

5) Treating chronic pain

I will briefly cover medications.

In general it is not a good idea to rely too heavily in medication. Psychotherapy has proven to be more effective in a larger number of patients. There are only 2 medications approved for PTSD, sertraline and paroxetine.  However, there is good evidence for venlafaxine and fluoxetine as well and these 4 medications are the first-line pharmacological treatments for PTSD. Higher doses and longer durations are often needed to get a response.

Nefasadone is a very useful second-line med, and would probably be considered a first-line treatment if not for rare liver toxicity. It’s sedating properties can help with insomnia.

Mirtazapine is useful, particularly as an augmentation to a first-line med. It’s sedative properties can help with sleep.

Prazosin has been useful for nightmares and a recent article in the American Journal of Psychiatry confirmed it’s benefits for nightmares and found that it improved overall symptom levels.

Medications that can be useful as add-ons but for which good evidence is lacking include buspirone, trazodone, bupropion, tricyclic antidepressants, and second-generation anti-psychotics (studies using risperidone have not found it to be helpful0.

There is general agreement that benzodiazepines should not be used alone, and if used for a co-morbid condition it is best to use them for short periods of time.

Anti-epileptic medications (with the possible exception of topirimate) and guanfacine have not been helpful.