Black box warning labels DECREASE suicide

No Significant increase since HUGE REDUCTION in SSRI Use!

SSRI's Increase Suicide Risk

 Recently people have been reporting that SINCE the anti-depressant medications have obtained a Black Box Warning Label, indicating they can CAUSE people to feel suicidal, there has been a significant reduction in the use of these drugs, there has been a 16-18% increase in suicides…due to not taking the medications.  THIS IS SIMPLY FALSE AND MISLEADING.

 While one obvious rebuttal for this antidepressant/suicide story is that correlation does not equal causation -- and researcher Dr. David Antonuccio, PhD makes a good point about neglecting to consider the increase in anti-psychotics for kids as the contributing factor for any increase observed (i.e. as well as  many other potential variables).  There is however, an even MORE GLARING REASON that Newsweek and other media should be ashamed of itself for suggesting this idea.  Read Below.
         
Only wishful thinking on the part of antidepressant manufacturers leads to a conclusion that the drop in SSRI prescriptions for 5-18 year old in 2004 has resulted in increased suicide for that age group. The researcher who told Newsweek that reduced antidepressant prescribing has led to more suicides in kids is on the advisory board of Eli Lilly (manufacturers of Prozac).  If one examines suicide rates for the entire period from 1999 to 2003, when antidepressant use for this age group was high, one sees that 2004 suicide rates are unremarkable.  According to official CDC statistics, the rate of suicide for CDC's 5-14 age group in 2004 is exactly the same rate as in both 2001 and 2000.  Similarly, the suicide rate for CDC's 15-24 age group in 2004 is actually slightly lower than the 2000 rate. Should there actually ever be a substantive increase in suicide rates, history tells us the likely source will not be a lack of psychiatric treatment but rather social or economic upheavals.

Sources:   If you would like to check out the actual CDC suicide statistics, I have the CDC links and tables demonstrating that suicide rates have not increased after the decrease in antidepressant prescriptions for 5-18 year-olds.

http://www.cdc.gov/nchs/data/nvsr/nvsr54/nvsr54_13.pdf
CDC's National Vital Statistics Report Deaths: Final Data 2003 (which includes data from 1999-2003)

http://www.cdc.gov/nchs/data/nvsr/nvsr54/nvsr54_19.pdf
CDC's National Vital Statistics Report: Deaths Preliminary Data 2004

Deaths per 100,000
Intentional self-harm
(suicide)             5-14 years        
2004                       0.7                               
2003                       0.6                   
2002                        0.6                 
2001                        0.7                          
2000                        0.7                   
1999                        0.6                  

Intentional self-harm
(suicide)             15-24 years
2004                       10.1            
2003                         9.7
2002                         9.9
2001                         9.9         
2000                       10.2
1999                       10.1
Intentional self-harm
(suicide)             All Ages       
2004                    10.8                      
2003                    10.8             
2002                    11.0             
2001                    10.8              
2000                    10.4             
1999                    10.5             

"Pharmacoepidemiological studies examining the relationship between trends in sales or prescription fills of SSRIs have consistently shown a relationship between increases in SSRI prescription rates and declines in adolescent suicide rates (9, 35–37). On the basis of those studies, one might expect that the adolescent suicide rate would begin increasing in the wake of the FDA advisory after a decade of steady decline. {p. 890}"

The Newsweek article stated prescriptions for pediatric depression (ages 5 - 18) dropped more than 50% between 2003 and 2005 -- a 2-year period. This is also not what the article in Am J. Psychiatry stated. Rather, it stated prescription rates for pediatric depression had been steadily rising since 1998, and that after the October 2003 black box warning prescription rates in October 2005 were 58% lower than they would have been had they continued to rise between October 2003 and October 2005 at the same average rate at which they had risen between October 1998 and October 2003. Using their figures, the actual decline in prescription rates for SSRIs for pediatric depression between October 2003 and October 2005 was 45.5%.

Then the article states that "in a parallel development, the number of teen suicides jumped a record 18% between 2003 and 2004." It mentioned no source. It did mention that the CDC will release suicide figures for 2005 in December of 2008. This leads me to believe that the Newsweek article used CDC above.

If they used the CDC data for the ages 5 - 14, using only one significant figure (we could use more than one) the increase between 2003 and 2004 is 0.7 / 0.6 = 16.67%.

In the 15 - 24 "teenager" age  group the increase between 2003 and 2004 is 10.1 / 9.7 = 4.1%.

I would expect to find more teenagers in this group than in the former, and would certainly expect a higher suicide rate in the latter group.When the two age groups are aggregated into one (5 - 24), there was no change, the rate remained 10.8 per 100000.  In this case a reversal from increases in suicide rates over time to no significant rate change over time. It isn't really a paradox. It is just the result of combining groups of different sizes and comparing aggregates with the separate groups. It looks as someone picked the group that best fit what they wanted and ignored the aggregate data. When discussing teen suicides I think that the 5 - 14 group is the least significant of the three.

Now this "18 % increase in teen suicides from 2003 to 2004" is being broadcasted all over the place as if it is an actual fact.

Tony Dokoupil’s Trouble in a ‘Black Box’ (July 16 article) importantly addresses the risks and benefits of prescribing antidepressants to children. However, the referenced study is far from “compelling” evidence for removing the FDA Black Box warning and such an interpretation of its findings is misleading.

 An inspection of this Eli Lily funded study reveals that the precipitous drop in SSRI prescriptions did not occur, as reported, from 2003 to 2005, but rather from February to October of 2005 (over 85% of the drop in the last 6 months of the reported time). The so-called “parallel development” of increased suicides occurred between 2003 and 2004—and therefore had no relationship to the drop in prescription rates reported in this study. Given that the decrease in prescription rates and increase in suicides occurred in different time periods, it begs the question of how such unsubstantiated statements could be made by the experts cited in the a rticle.

Only 3 of 15 clinical trials have shown antidepressants to be superior to a sugar pill on primary measures. Children and parents in those 15 studies reported no advantage of antidepressants over a sugar pill.

Data from the FDA and its British counterpart demonstrate that children and adolescents taking antidepressants are twice as likely to experience suicide-related events. Given the meager results and increased risk for suicide-related events (as well as other serious adverse events), antidepressants are not a good choice for youth struggling with depression—a conclusion reached after an extensive risk/benefit analysis conducted by the American Psychological Association’s Work Group on Psychotropic Medication (e.g first choice).

Given that depression tends to remit over time, and so suicidality, do these studies really prove anything other than that any possible increase in suicidality caused by the medications is insufficient to overwhelm the natural average decrease in suicidality expected to be seen in any depressed population over time?

Barbui, C., at el, 2008, Paroxetine (Paxil) not superior to placebo (sugar pills) amount adults with major depression, In Canadian Medical Association Journal, Jan. 29. Among adults, paroxetine was not superior to placebo (sugar pill) in terms of overall effectiveness.  Researchers undertook a systematic review of published and unpublished clinical trial data to determine the effectiveness and acceptability of Paxil. The researchers searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the Glaxo-SmithKline Clinical Trial Register, MEDLINE and EMBASE up to December 2006. Published and unpublished randomized trials comparing paroxetine with placebo in adults with major depression were eligible for inclusion. The research team included 29 published and 11 unpublished clinical trials in their review, with a total of 3,704 patients who received paroxetine and 2,687 who received with placebo. Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44-2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17-5.54).  Thus, if your depressed and an adult, taking Paxil instead of just a sugar pill increases your odds of becoming suicidal by 2.5 times.  CMAJ 2008;178(3):296-305.

Fava, G.,Journal of Clinical Psychiatry 64:2, February 2003 page 123-133. This was forwarded to me by Dr. Gary Kohls, MD.  Thank you Gary.
Long-term use of antidepressant drugs may increase biochemical vulnerability to depression and worsen the long-term outcome and symptomatic expression of the illness, decreasing both the likelihood of subsequent response to pharmacologic treatment and the duration of symptom-free periods.The findings of this article call for a more cautious attitude among clinicians in prescribing antidepressant drugs, because these drugs may worsen the course of depression. A statistical trend suggested that the longer the drug treatment, the higher the likelihood of relapse. Systematic treatment with tricyclic antidepressants has proved to be associated with an increase in the total number of recurrences. In a recently randomized, double-blind crossover study comparing the effects of Remeron and Zoloft in 20 healthy volunteers, 2 subjects reported becoming depressed and 2 others reported becoming suicidal, a dramatic incidence of 20% serious depression, obviously caused by the drugs. Another trial for panic disorder comparing an antidepressant, (imipramine) cognitive-behavioral therapy (CBT) or a combination of the two modalities resulted in much higher 6 month response rates with the CBT plus placebo (41%) than CBT plus drug (26%).

The occurrence of mania in depressed patients upon treatment with antidepressant drugs is a relatively old clinical observation, even with the use of “mood stabilizers.” Antidepressants may double the incidence of a switch into mania (50% in some cases) compared with placebo (25% of cases). Antidepressant-induced mania is not simply a temporary and reversible phenomenon, but a complex biochemical mechanism of illness deterioration.

The return of depressive symptoms during maintenance antidepressant treatment was found to occur in 9% to 57% of patients in published trials. Possibilities include pharmacologic tolerance, loss of placebo effect, increase in disease severity, change in disease pathogenesis, accumulation of a detrimental metabolite, unrecognized drug-induced mania and prophylactic inefficacy.  Discontinuation of antidepressant drugs may trigger hypomania or mania despite adequate concomitant mood-stabilizing treatment. Mood elevation may also occur by decreasing the antidepressant dose.

Processes that change the number or properties of drug-sensitive receptor populations, have very limited explanatory power in terms of the clinical phenomena previously described.  A therapeutic action of antidepressant drugs (e.g., down-regulation of postsynaptic 5-HT2 receptors) may, under certain conditions, trigger changes in post-receptor signal transduction, in intraneuronal signaling pathways, or in neuronal architecture that are likely to affect the balance of serotonin receptors.

Impairment in neurogenesis may be the key pathophysiologic event in depression. Antidepressant drugs may yield changes in connections or sensitivity to neurotransmitters indirectly related to the specific actions.

Both sensitization to stressors and episode sensitization may occur in mood disorders and become encoded at the level of gene expression. Stressors and the biochemical concomitants of the episode can themselves induce the proto-oncogene c-fos and related transcription factors, which then affect the expression of neurotransmitters, receptors, and neuropeptides that alter responsiveness in a long-lasting way.

The use of antidepressant drugs is so prevalent that it is difficult to recruit clinical populations who have never been exposed to them!  CBT appears to reduce the risk of depressive relapse and may have a more durable effect than pharmacotherapy alone.

Researchers thus should demonstrate that the combination of psychotherapy and pharmacotherapy is inferior in terms of relapse prevention to psychotherapy alone. Patients with past antidepressant treatment had more episodes of depression and a longer duration of illness.

We strongly suspect that many patients who are simply unhappy receive these drugs, with predictable consequences in terms of morbidity from side effects, mortality from overdose, economic waste, and irrational, unproductive clinical management.  A treatment that is helpful on average may be harmful for some patients, as shown by a re-analysis of the Beta-Blocker Heart Attack Trial.

Certainly, researchers working along these lines are likely to encounter tremendous difficulties in disclosing their results in journals and symposia or in getting their studies started and funded, in view of the current ideological and pharmaceutically driven climate.  We should be aware that we are stretching the original indications (major depressive episodes) of drugs of modest efficacy to include prevention of relapse, anxiety disorders and demoralization. Antidepressant drugs may speed improvement and change the boundary between “responders” and “non-responders.” However, when we prolong treatment to more than 6 to 9 months, we may recruit different phenomena, such as tolerance, episode acceleration, and paradoxical effects.   Excerpting, some paraphrasing  and underlining by Gary G. Kohls, MD, Duluth, MN.

Maurizio Fava et al have published a very important paper in J Clin Psych 2006;67:1754-1759. They found that >30% of patients on long-term antidepressants were found to have cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowness) and 40% have physical symptoms of fatigue and sleepiness and sedation. The authors thought it was likely that the symptoms were both residual symptoms of depression and side effects of medication.  Thus, if you take an anti-depressant, 30+% will have symptoms of ADHD as a result of the drug.  Therefore, be careful you are not given a second diagnosis and another medication to get rid of the side effect from the first medication.

Wheeler, B. from the University of Bristol, in the United Kingdom, was published online February 14, 2008 in British Medical Journal.   Reduced prescribing of selective serotonin reuptake inhibitor (SSRI) antidepressants for young people in the United Kingdom following regulatory action in 2003 did not lead to an increase in suicidal behavior, according to an ecological time series study. They analyzed 3 sets of data from 1993 to 2006: antidepressant prescriptions for 12- to 19-year-olds in the United Kingdom, annual deaths from suicide in 12- to 17-year-olds in England and Wales, and hospital admissions for self-harm in 12- to 17-year-olds in England.  They found that among young people, antidepressant prescribing doubled from 1999 to 2003 and then dropped back to the 1999 level by 2005. Deaths from suicides, however, declined annually from 1993 to 2005, and the rate of hospital admission for self-harm remained relatively stable. "These data for England do not indicate that reductions in antidepressant use have led to an increase in suicidal behavior," the group writes.  The findings differ from those of Gibbons and colleagues, who reported that mortality rates for suicides in 5- to 19-year-olds in the United States increased in 2004, the year following regulatory action (Gibbons RD et al. Am J Psychiatry 2007;164:1356-1363), said Dr. Wheeler. More recent critiques of that study, however, suggest that the US situation may not actually differ that much from the United Kingdom's, he noted (Letters to the editor. Am J Psychiatry 2007;164:1907-1910).