Medicating childhood
Trends in prescriptions for stimulants in England
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1992 1996 2000 2004 2008
antidepressantprescriptions(millions)
Trends in antidepressant prescribing 1992-2010
• “People with depression may have an imbalance of the brain’s neurotransmitters” Eli Lilly, 2003
• “Paxil CR helps balance your brain’s chemistry” PaxilCR.com, 2009
Models of drug action
Disease centred model Drug centred model
Drugs correct an abnormal brain state
Drugs create an abnormal brain state
Drugs as disease treatments Psychiatric drugs as psychoactive drugs
Therapeutic effects derived from effects on (presumed) disease pathology
Useful effects are a consequence of the drug induced state
Paradigm: insulin for diabetes Paradigm: alcohol for social anxiety
Psychoactive drugs
• Produce altered mental and physical states
• Tolerance and withdrawal effects
Classification of psychiatric medications
Pre 1950s:
• Sedatives
• Stimulants
Post 1950s:• Antipsychotics• Antidepressants• Anxiolytics• Mood stabilisers• Hypnotics
• No evidence that psychiatric drugs reverse underlying chemical imbalances or other biological abnormalities
Different assumptions- different values
Disease centred model- assumes benefit
Drug centred model- assumes harm
So how do psychiatric drugs work? The drug-centred model
• Direct effect of psychoactive and physical effects
• Amplified placebo effects
Using drugs in a drug-centred manner
Need to know full range of:• Mental effects• Physical effects• Short-term effects• Long-term effects• Withdrawal effects
and…• Are the effects a drug produces useful in an individuals
particular situation?
• Do useful effects persist with continued use?
• Do they out-weight the adverse effects?
• Are there alternatives?
• Diagnostic independent practice
Effects induced by stimulant drugs (Ritalin, amphetamine, atomoxetine, etc)
• Increase attention on repetitive tasks• Suppress exploratory, inquisitive and social
behaviour• Stereotypic behaviours or perseveration
• May improve attention to simple tasks in short-term• No evidence that they improve performance on
complex tasks or over long-term
Evidence for stimulants in childhood ADHD – placebo controlled trials
(Schachter et al, 2001)
• Short-term improvement of attention and reduction of hyperactivity
• But trials of poor quality and evidence of publication bias
• Longest trials – 6 months- showed no effect
MTA study• 14 months: some positive outcomes for children randomised to
‘medication management’ (inattention, parents and teachers, hyperactivity parents only; none for blinded independent rater)
• No differences in academic achievment, aggression, parent-child relations and social skills
• 3 years no difference between children randomised to ‘medication management’ vs others, or between stimulant-treated children and others
• 8 years- no differences
Adverse effects of stimulants
• Growth restriction (4cm in MTA study at 3 years)
• Raise blood pressure, pulse, and associated with sudden cardiac death
• Psychological effects: ‘zombie’ effect, psychosis, depression
•
Psychoactive effects of some modern antidepressants (SSRIs and venlafaxine)
• Drowsiness, lethargy• Cognitive impairment• Emotional blunting• Reduced libido
• Agitation and anxiety• Tension• Insomnia• Anger, Aggression, Emotional instability• Impulses to self harm/suicide
• Not pleasant for volunteers
Evidence on utility of antidepressants in children
• Efficacy of antidepressants in adults not demonstrated because of ignoring of psychoactive effects and amplified placebo effects.
• Differences between antidepressants and placebo in children small (mean change 3.51 on a scale from 17-113) (Hetrick et al, 2012 Cochrane review)
• Increased suicidal thoughts and behaviour repeatedly demonstrated
• May set up lifelong psychological dependence on medicines
Patient information
• The antidepressant will help normalise your serotonin levels
• The antidepressant will improve your depression
• This drug affects the way people think and feel (not just people with depression), but we are not sure how. It may dampen down your emotions, suppress your libido and make you feel a bit lethargic….
Community antipsychotic prescriptions 1998-2010 (PCA)
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4
5
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8
1998 2000 2002 2004 2006 2008 2010
antipsychoticprescriptions(millions)
National trends in office-based visits by children and adolescents that included antipsychotic treatment, 1993-2002 (Pincus et al, 2006)
• ‘antipsychotic medicines are believed to work by balancing the chemicals found naturally in the brain’
Eli Lilly, zyprexa.com, 2011
Antipsychotics
• Physical and mental suppression (similar to Parkinson’s disease for older drugs)
• Emotional dampening or indifference
• Used as animal tranquillisers
Early intervention in psychosis ‘movement’
• Early intervention• Early detection• Prevention of psychosis
• Justified by ideas about duration of untreated psychosis and neurodegeneration
Symptom Examples
Social withdrawal Spending more time alone
Avoiding friends and family
Avoiding groups
Functional decline Dropping grades
Missing classes, school, or work
Not responding to friends
Behavior changes Collecting objects or hoarding
Developing a new and unusual interest
Developing an odd habit or gesture
Taking risks
Concentration difficulty
Having trouble focusing or paying attention
Losing abilities in athletics or hobbies
Losing track of conversations
Forgetting
Getting lost
Developing difficulty with homework, reading, and understanding long sentences
Loss of motivation or energy
Quitting sports, groups or clubs
Declining interest in previously enjoyable activities
Sleeping more
Spending more time inactive
Staying home from school
Dramatic sleep and appetite changes Eating more or less than usual
Sleeping more or less than usual
Eating only certain foods
Suspiciousness of others
Worrying about what others are thinking
Thinking others wish to harm you in some way
Watching others with suspicion
Feeling fearful or uneasy around people
Unusual or exaggerated beliefs about person powers or influences Thinking you have special or magical powers
Believing or fearing you can influence others without their knowledge
Believing someone is putting thoughts in your brain
Castle, 2012
• WHO estimate: 14 new cases of psychosis per 100,000
• Cambridge (England) Early Intervention service 50 per 100,000
• Melbourne (Australia) Early psychosis programme approx 100 per 100,000
Trials of early intervention
• OPUS study n=547
• Lambeth Early Onset study n=144
• Some benefits while intervention active. Neither showed any specific benefits from starting antipsychotics early, nor any benefits after intervention ceased
Prevention of psychosis- high risk mental state
• Early estimates: 40% proceed to psychosis
• Latest estimates 8-20% (Australian group 13% in latest trial)
Prevention of psychosis-drug trials
• McGorry et al, 2002: 3X lower risk of developing psychosis
• McGlashan et al, 2006- no sigt difference
• Ruhrmann et al, unpublished
• McGorry et al, 2012- no sigt difference
Early intervention and the pharmaceutical industry
Bipolar symptoms test
The Zyprexa papers
• ‘Complex mood disorder’
Paediatric bipolar disorder
New York Times, 2008