Psychopharmacology for Clinicians

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Psychopharmacology for Clinicians

• Professor Peter Hill
• London

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General principles

• Use drugs as part of overall plan
• Consider symptoms rather than disorders
• Consult widely the published evidence is often
  weak
• Titrate doses rather than mg/kg
• Be aware most drugs are not licensed

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Titration

• Children have very effective livers much of an
  oral dose is lost on first pass metabolism
• Be clear about goals. Dont be satisfied with
  just some improvement
• Find a way of measuring improvement, possibly a
  rating scale

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School

• Best if fully involved
• Need information. Problem getting all teachers in
  secondary/high schools involved
• Stimulants need only be given on schooldays

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Drugs to know

• methylphenidate/dexamphetamine
• atomoxetine
• SSRIs
• imipramine
• clonidine
• sedative antihistamines
• benzodiazepines

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Drugs to be aware of

• clomipramine
• propanolol
• risperidone
• other antipsychotics
• mood stabilisers

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Methylphenidate (MPH)

• Stimulates many mental functions by blocking
  dopamine transporter
• (i.e.re-uptake blockade at synapse)

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At the (midbrain) synapse
presynaptic
postsynaptic
dopamine
D4 receptor
dopamine transporter recovers DA to presynaptic
neurone
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At the synapse
Excess dopamine transporter in about half of all
cases Dougherty et al. 1999
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At the synapse
Excess dopamine transporter in about half of all
cases Dougherty et al. 1999
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Methylphenidate (MPH)

• Stimulates many mental functions by blocking
  dopamine transporter (i.e.re-uptake blockade at
  synapse)
• Can do this in normal children (abuse by
  parents?)
• Not addictive in ADHD treatment
• Sustained release preparations popular (school
  not involved - not a good thing?)

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Methylphenidate (MPH)

• Onset insomnia
• do not give too late in the day
• problems with evening behaviour/homework
• can add evening clonidine (ECG first), melatonin,
  sedative antihistamine
• Growth problems infrequent with immediate release
  (Ritalin, Equasym), unknown frequency with
  sustained release preparations (Concerta XL,
  Equasym XL)

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Methylphenidate (MPH)

• Titration
• Can start with am dose, contrast am vs pm
• Otherwise aim for 3-3.5 hr intervals
• 5,5,5 (2.5) (8.00, 11.30, 3.00, (5.00)
• 10,10,5/10
• 15, 15, 15 (5-10)
• Or Concerta XL 18 then 36 etc.
• or Equasym XL?

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Dexamphetamine

• very slightly longer duration than MPH
• adverse effects generally trickier to handle
• euphoria and misuse more of a problem
• dose is half that for MPH
  (5mg10 mg MPH)
• Adderall (dexamphetamine salts) is essentially
  the same

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Atomoxetine

• non-stimulant (?) ADHD treatment
• blocks norepinephrine transporter, especially in
  frontal lobes
• no insomnia though some reduced weight gain with
  growth in first 12 months of use
• likely to be non-controlled

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Selective serotonin re-uptake inhibitors (SSRIs)

• fluoxetine
• sertraline
• paroxetine
• citalopram
• escitalopram
• fluvoxamine

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Selective serotonin re-uptake inhibitors (SSRIs)

• differ from each other mainly in adverse effects
• helpful in depression, anxiety, obsessive
  compulsive symptoms
• may help self-injurious behaviour in severe
  learning disability and autism
• a few children become silly and socially
  disinhibited
• muddle over MHRA proscription

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Imipramine

• useless antidepressant
• outclassed by desmopressin in enuresis
• not much good with anxiety
• moderately effective in ADHD

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Clonidine

• moderately useful in ADHD, especially
  hyperactivity and hostility, can use in evening
• first line in Tourettes disorder (but often
  ineffective)
• post-traumatic stress disorder
• self-injurious behaviour in autism
• sleep problems (though can produce insomnia and
  nightmares in a few)

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Clonidine

• is a noradrenergic agonist at ?2 receptors
• ?2 receptors mainly in
• locus coeruleus (main NA centre in brainstem with
  widespread activating projections to cortex)
• prefrontal cortex

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Pre-synaptic and post-synaptic a2 receptors
NA feedback
clonidine
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Presynaptic NA agonism (locus coeruleus)inhibits
NA release by activating autoreceptor
NA feedback
clonidine
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Postsynaptic NA agonism (pre-frontal cortex)
activates by simulating NA release
clonidine
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Clonidine

• start low, go slow
• monitor BP, pulse rate (and ECG?)
• warn parents not to stop abruptly
• drowsiness main problem, wears off after 10 days
  until ceiling at about 200-300 mcg daily

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Sedative antihistamines

• widely used for sleep onset problems
  (diphenhydramine, promethazine,
  hydroxyzine,alimemazine/trimeprazine)
• unlikely to help child with anger or anxiety
  symptoms

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Benzodiazepines

• rapid tranquillisation (lorazepam)
• panic attacks (alprazolam)
• may cause paradoxical excitement or dysphoria
• best used for brief periods only

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Clomipramine

• tricyclic antidepressant with serotonin re-uptake
  blocking action
• powerful in OCD
• difficulty with adverse effects
• constipation
• dry mouth
• blurred vision
• postural hypotension

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Risperidone

• reduces aggressive behaviour and rage
• reduces tics
• looks useful in ADHD symptoms in PDDs
• relatively low risk of extra-pyramidal effects
  but a few dribble
• weight gain a problem

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Other antipsychotics

• haloperidol for tranquillisation and tics
• phenothiazines (chlorpromazine etc) for
  short-term tranquillisation, otherwise best
  avoided because of extra-pyramidal complications
• olanzapine increasingly popular but weight gain
  and sugar/fatty acid problems

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Mood stabilisers

• mainly carbamazepine, valproate
• lithium less commonly because of
• thyroid and renal problems
• blood level monitoring needed

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Future?

• more use of medication in child mental health
  problems
• more children with mental health problems that
  specialist child psychiatric services can manage
• non-specialists likely to be come involved as
  prescribers