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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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