Prescribers and parents in the UK and US were dismayed when national regulatory bodies issued warnings about the class of antidepressants known as SSRIs (selective serotonin reuptake inhibitors).  In the UK, government reports stated that these drugs are largely ineffective in children for treating major depression and can cause suicidal behavior and self-harm. 

Why don’t these drugs have their safety established before they are available and used?  One reason is that the duration of a drug trial is an average of 6-8 weeks, but depression is treated for much longer.  Secondly, populations studied before drugs are released are highly restrictive and not representative of the likely recipients of these drugs.  Not least, manufacturers who receive reports of adverse drug reactions are not required to report them and there is evidence that the public never learns about many of these adverse reactions. 

Pharmaceutical companies are not required to release pre-market trial results that show “no effects” after testing a drug.  There are high placebo response rates for many psychiatric disorders (e.g., Paroxetene or Paxil has shown to benefit for 69% of patients, but placebo worked for 59%).  Aside from depression, SSRIs are used to treat obsessive-compulsive disorders, social phobias, and generalized anxiety – none of these are official indications for these drugs.  (See this issue’s article, titled: Childhood Anxiety Disorders)

The public has no way of knowing whether the SSRIs were ever proven to be ineffective for these disorders.  As adverse reactions found with these drugs when being tested for non-indicated disorders are never reported, prescribers must assume that adverse reactions are somewhat similar to the adverse reactions when the medication is being used for depression, an indication for using the drug.  Why are these drugs given for non-indicated disorders?  Many children suffer without therapy.  Doctors do their best to weigh benefits versus risk – even without all the available evidence known to them.  To help doctors weigh risk-benefits, British regulators announced in 2003 that the risk-benefit ratios for all SSRIs in childhood were unacceptable, excepting for the drug fluoxetine (also known as Prozac or Sarafam). 

(Herxhimer A, Mintzes  B. Can Med Assoc J 2004; 170(4):487-489)
(Garland EJ.  Can Med Assoc J 2004; 170(4):489-491)

Comment:  After the British warning, the U.S Federal Drug Administration (FDA) issued an advisory that further cautions physicians, patients, and their families.  They recommend that  adults and children should be closely monitored at the beginning of treatment and whenever the doses are changed. The FDA is asking manufacturers to change the labels of 10 drugs.  They want them accompanied by stronger cautions and warnings about depression and the emergence of suicidal ideation.  Their web site is at:  http://www.fda.gov    - H.T.