Bioidentical Hormones 101 
The Book, by Jeffrey Dach MD

Chapter 37. SSRI Antidepressants No Better Than Placebo Says JAMA

SSRI Antidepressants No Better Than Placebo Says JAMA Chapter 37. SSRI Antidepressants Are No Better Than Placebo, Says JAMA

Getting Off SSRI Anti-Depressant Drugs

Left Image: Sad Face Icon, courtesy of Tango Desktop Project and Wikimedia Commons

A study published in JAMA on Jan 5, 2010 reported that SSRI antidepressants are no better than placebo for most cases of depression.(1) The authors reviewed 30 years of data and concluded that:

"the benefit of antidepressant medication compared with placebo may be minimal or nonexistent in patients with mild or moderate symptoms". 

Of course, this is old news, and reminds me of the famous scene in 1942 film, Casablanca starring Humphrey Bogart and Ingrid Bergman where the game is always rigged.  When Rick asks, “why is the casino being closed down”?  The French Captain replies with the famous line: " I am Shocked, Shocked ... to find gambling here....Here are your winnings... Oh thank you."  You must see the video clip on You Tube. (12)

Better than Placebo for Severe Depression

I should add that the study found SSRI antidepressants work better than placebo for severe depression.  This is not surprising, since virtually any psycho-stimulant can be found useful for the most severely depressed patient. 

Is Depression Really a Medical Disease?

Medically speaking, the term "Depression" is a vague constellation of feelings and symptoms scored by a questionnaire called the Hamilton Depression Score.  There are a number of handy on-line tools for taking the Hamilton Depression Score Questionnaire.  For the short 17-item version of the Hamilton questionnaire, scores can range from 0 to 54.   Hamilton scores between 0 and 6 are normal.  Scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.  According to the Jan 5 JAMA study, if the Hamilton score is less than 24, then placebo is just as effective as SSRI antidepressant drugs.  That means the SSRI drug is as effective as a sugar pill called a placebo.

Hamilton Depression Score Questions (short version):


Are you sad, hopeless, helpless, worthless?

Feeling of Guilt

Do you have feelings of guilt, or self reproach?


Do you have Suicide ideas, gestures or attempts?


Do you have difficulty falling asleep, staying asleep?

Work and Activities

Do you have thoughts and feelings of fatigue or weakness? related to activities,  or decreased or stopped activities or working because of present illness? 


Do you have Slowness of thought and speech; Do you have difficulty concentrating; slow movements?


Do you have Fidgeting,  Playing with hands, hair, etc,  Moving about, can't sit still.  Hand ringing, nail biting, hair-pulling, biting of lips etc?


Do you have tension and irritability, Worrying,  Apprehension, Fears expressed?


Do you have dry mouth, wind, indigestion, diarrhea, cramps, belching. - Cardio-vascular : palpitations, headaches. hyperventilation, sighing. Urinary frequency - Sweating?


Do you have loss of appetite, require laxatives or medication for bowels, or medication for gastro-intestinal symptoms?


Do you have Heaviness in limbs, back or head? Backaches, headache, muscle aches. Loss of energy and fatigability?


Do you have loss of libido, menstrual disturbances?


Do you have preoccupation with  your health?


Do you have weight loss from depression?


Acknowledges or denies being depressed  ?

Overlapping Symptoms- Is it Really Depression?

As is obvious, many of these feelings or symptoms are somewhat subjective and rather vague, so depression scoring is not an exact science and can be manipulated according to the agenda of the research or questioner. As you can see, many of these Hamilton symptoms overlap with real medical diseases.  For example, inflammatory bowel disease patients would score positive for the GI symptoms even though they may not be clinically "depressed".  Somatic symptoms of fatigue and muscle pain may overlap with fibromyalgia and hypothyroid symptoms.  Slowness of thought and speech could overlap with a low thyroid condition or a neurological disorder such as B12 deficiency.  Patients in chronic severe pain contemplating suicide may not necessarily indicate clinical "depression".  Obviously, these patients need pain relief rather than an SSRI antidepressant.

Hormonal Imbalance Symptoms Overlap with Many of the Hamilton Symptoms

Many women with hormonal imbalance related to pre-menopause  or post menopausal transitions will have mood disorders and symptoms which overlap with many of the symptoms on the Hamilton Depression Score.  For example, estrogen deficiency is a well known cause of anxiety, a symptom listed on Hamilton Depression Score.   However, it would be a mistake to treat a woman with estrogen deficiency with an SSRI antidepressant. 

The syndrome Premenstrual Dysphoric Disorder is commonly treated by mainstream physicians with SSRI antidepressants. (39)  This is an error, and a practice that should be halted.   These patients would be best served by treating them with progesterone, the hormone missing in this disorder.  With the Jan 5, 2010 JAMA article, we now have evidence that Premenstrual Dysphoric Disorder and other common forms of hormonal imbalance are poorly served by SSRI antidepressants.  Using SSRI's is simply the wrong way. The benefit of SSRI antidepressants for this group is the same as the benefit from placebo. Rather than give them SSRI antidepressants, this group of women with PMS, estrogen deficiency or progesterone deficiency should be properly evaluated, and then treated with bioidentical hormones to address their underlying problem.  We have noted considerable success using cyclic natural progesterone in this group of women with PMS and other hormonal imbalances.  In my opinion, natural progesterone is a far better form of treatment with none of the adverse side effects associated with SSRI antidepressants.

Adverse Side Effects of Antidepressants - Placebos Have NONE

When SSRI antidepressants are found equally effective compared to placebo, the next question relates to adverse side effects.  By definition, placebos have no adverse side effects.  However, this is not true for SSRI antidepressants which have the following adverse effects:  Sexual dysfunction, weight gain and sleep disturbance are the most troubling adverse effects of SSRI anti-depressant therapy.(42-44) The most common side effects associated with SSRI antidepressants are nausea, headache, nervousness, insomnia and sexual dysfunction.  When I examine these patients in my office, they usually demonstrate dilated pupils and hyperactive reflexes.  The long term SSRI users may have irreversible neurological changes, and many are simply “burned out” from chronic over-stimulation of the nervous system. 

SSRI Antidepressants and Suicide Risk

Another troubling adverse effect of SSRI antidepressants is increased suicide first reported by Teicher in 1990.(40)  According to David Healy’s book, “Let Them Eat Prozac”, the original clinical trial data was manipulated by moving the suicide cases from the treatment arm over to the placebo arm of the study.(41)  This manipulated data was then submitted to the FDA who conveniently looked the other way.  This disturbing information was presented at a Cornell University Mar 25, 2009 talk by David Healy which can be seen on a You Tube video.(42)

The Army and Military Suicide from SSRIs Antidepressant Use

Another striking finding is the unprecedented increased suicide rate in the military with widespread use of SSRI's and other psycho active drugs in the Army.   Again this is a rather sad commentary, and another nail in the coffin for SSRI drugs as more harmful than helpful.(34-36)

For references and links, see my web site:

References for Chapter 37. SSRI Antidepressants No Better Than Placebo Says JAMA

Antidepressant Drug Effects and Depression Severity A Patient-Level Meta-analysis by Jay C. Fournier et al. JAMA. 2010;303(1):47-53. 

Initial Severity and Antidepressant Benefits: February 26, 2008 A Meta-Analysis of Data Submitted to the Food and Drug Administration. Irving Kirsch et al.

(3) Depression treatment: We need better not simply more Getting more people into treatment for depression is not enough . Psychology Today. January 5, 2010

(4) New York Times. Popular Drugs May Help Only Severe Depression By BENEDICT CAREY. January 5, 2010

Wall Street Journal . Jan 6, 2010.Effectiveness of Antidepressants Varies Widely By Jennifer Doorden

(6) Study Shows Antidepressants Work Best for Severe Depression, Provide Little to No Benefit Otherwise. January 05, 2010

Antidepressants Don’t Help Mild Depression: Study . Pharmalot.

Online Hamilton Depression Score.  17- item version of Questionnaire

On-Line Hamilton rating scale for depression 17 questions

online HMD questionaire -  quick score for depression - adjusted for layman

online HMD questionaire -  quick score for depression - classic printable version

(12) //
Casablanca is a 1942 film - Captain Louis Renault. I am shocked — shocked— to find that gambling is going on in here!

(13) Problems associated with long term treatment with selective serotonin reuptake inhibitors by Chantal Moret and Mike Isaac

The Antidepressant Dilemma - antidepressants have limited-to-zero efficacy for those with mild depression.

Antidepressants Don’t Help Mild Depression: Study By Ed Silverman. January 5th, 2010

(16) Furious Seasons :Study: Anti-Depressants Ineffective For Mild, Moderate Depression

Antidepressants Hardly Help By Laura London  Feb. 26, 2008 Time Magazine

(18) Antidepressant-Placebo Debate in the Media- Balanced Coverage or Placebo Hype?

(19) Burne, J. (2002, June 20). Make-believe medicine. The Guardian.

(20) Gaudiano, B. A., & Herbert, J. D. (2003). Methodological issues in clinical trials of antidepressant medications: Perspectives from psychotherapy outcome research. Psychother Psychosom 2005;74:17–25 .

(21) Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the national comorbidity survey. Archives of General Psychiatry, 51, 8-19.

(22) Khan, A., Leventhal, R. M., Khan, S., & Brown, W. A. (2002). Severity of depression and response to antidepressants and placebo: An analysis of the Food and Drug Administration database. Journal of Clinical Psychopharmacology, 22, 40-45.

(23) Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 5, art. 23.

(24) Kirsch, I., & Sapirstein, G. (1998). Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment, 1, art. 0002a. Retrieved February 1, 2003, from

(25) Klein, D. F. (1998). Listening to meta-analysis but hearing bias. Prevention & Treatment, 1,

(26) Leber, P. (2000). The use of placebo control groups in the assessment of psychiatric drugs: An historical context. Biological Psychiatry, 47, 699-706.

(27)  Leuchter, A. F., Cook, I. A., Witte, E. A., Morgan, M., & Abrams, M. (2002). Changes in brain function of depressed subjects during treatment with placebo. American Journal of Psychiatry, 159, 122-129.

(28)   Mayberg, H. S., Silva, J. A., Brannan, S. K., Tekell, J. L., Mahurin, R. K., McGinnis, S., & Jerabek, P. A. (2002). The functional neuroanatomy of the placebo effect. American Journal of Psychiatry, 159, 728-737.

(29) Moore, T. J. (1999, October 17). No prescription for happiness. Boston Globe, E01.

(30)  Moncrieff, J., Wessely, S., & Hardy, R. Active placebos versus antidepressants for depression (Cochrane Review). The Cochrane Library, Cochrane Database Syst Rev. 2004;(1):CD003012.

Quitkin, F. M., Rabkin, J. G., Gerald, J., Davis, J. M., & Klein, D. F. (2000). Validity of clinical trials of antidepressants. American Journal of Psychiatry, 157, 327-337.

Rosenthal, R. (1979). The "file drawer problem" and tolerance for null results. Psychological Bulletin, 1979, V86, 638-641.

(33) Vedantam, S. (2002, May 7). Against depression, a sugar pill is hard to beat. Washington Post

America's Medicated Army- By Mark Thompson Thursday, Jun. 05, 2008 

R.D. Gibbons, C.H. Brown, K. Hur, S.M. Marcus, D.K. Bhaumik, and J.J.
Mann, "Relationship Between Antidepressants And Suicide Attempts: An Analysis of the Veterans Health Administration Data Sets," American Journal of Psychiatry 164 (2007): 1044-1049.

(36)  Valenstein M, Kim HM, Ganoczy D, McCarthy JF, Zivin K, Austin KL, Hoggatt K, Eisenberg D, Piette JD, Blow FC, Olfson M. Higher-risk periods for suicide among VA patients receiving depression treatment: prioritizing suicide prevention efforts. Journal of Affective Disorders, 2009 Jan;112(1-3):50-8.

(37) M. Raja, A. Azzoni, and A.E. Koukopoulos, "Psychopharmacological treatment before suicide attempt among patients admitted to a Psychiatric Intensive Care Unit," Journal of Affective Disorders 113 (2009): 37-44.

(38)  Peter R. Breggin, Antidepressant-induced suicide, violence and mania: Risks for military personnel,Journal The International Journal of Risk and Safety in Medicine , Volume 22, Nu

(39) Diagnosis and Treatment of Premenstrual Dysphoric Disorder by SUBHASH C. BHATIA, M.D., and SHASHI K. BHATIA, M.D. Am Fam Physician. 2002 Oct 1;66(7):1239-1249.

(40) Am J Psychiatry 1990; 147:207-210 Emergence of intense suicidal preoccupation during fluoxetine treatment . MH Teicher, C Glod and JO Cole

(41) Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression by David Healy, NYU Press (June 1, 2004)

(42) // The Future of Medical Care.  David Healy, psychiatrist and Cardiff University professor addresses the question: Can Industrialized and Marketized Healthcare be Made Universally Available? (Mar 25, 2009 at Cornell University)

(43) Prim Care Companion J Clin Psychiatry. 2001 February; 3(1): 22–27.SSRI Antidepressant Medications: Adverse Effects and Tolerability by James M. Ferguson, M.D.

(44) J Psychopharmacol. 2009 Nov;23(8):967-74. Problems associated with long-term treatment with selective serotonin reuptake inhibitors. Moret C, Isaac M, Briley M.

Author: Dr Dach

Jeffrey Dach MD

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