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instead. Other clinicians still choose stimulants as their first-line treatment
for ADHD in those with tics, using low to moderate doses if possible, and
watching carefully to see whether tics worsen.
Atomoxetine
This is an alternative to the stimulants. It is an inhibitor of the nora-
drenaline transporter, thereby raising synaptic levels of noradrenaline –
but also indirectly increasing dopamine levels in the frontal cortex. It has
a smaller average effect size than the stimulants (around 0.6 standard
deviations) and it takes longer to become effective (2-6 weeks). It is often
used as a second-line treatment when stimulants have not worked or have
had unacceptable adverse effects. Atomoxetine can have adverse effects of
its own, including nausea and sedation.
Alpha-2 agonists
Clonidine and guanfacine are specific alpha-2 agonists that can reduce
the symptoms of ADHD and tics, and may sometimes be the treatment
of choice for the combination of tics and ADHD. While clonidine has
been around for longer, guanfacine is often preferred nowadays because
it causes less sedation and does not result in rebound hypertension after
withdrawal. Alpha-2 agonists generally have a smaller effect size than
stimulants for ADHD and a smaller effect size than neuroleptics for tics,
but they may nevertheless be useful for either ADHD or tics when other
medications have failed or resulted in unacceptable adverse effects. Par-
ticularly in the treatment of tics, affected individuals and their families
may prefer a lesser reduction in symptoms from guanfacine to a greater
reduction from neuroleptics – making this choice in order to avoid serious
neuroleptics adverse effects such as dyskinesias (from typical neuroleptics)
or weight gain and metabolic disturbance (from atypical neuroleptics).
Tricyclic antidepressants (TCAs)
Nocturnal enuresis can be treated with low to moderate doses of TCAs
(for example, 25–75 mg of imipramine nocte), though it is almost al-
ways preferable to use a behavioural approach or desmopressin instead
(see Chapter 17). ADHD can also be treated with low doses of TCAs if
stimulants have failed or are contraindicated (see Chapters 5 and 13).
In full dosage, clomipramine (a TCA that acts primarily on serotonin
reuptake) has been shown to be helpful for obsessive-compulsive disorder
(see Chapter 14). Judging largely from adult evidence, TCAs may also be
useful in panic disorder. Meta-analyses do not support the use of TCAs in
the treatment of depressed children and adolescents.
In the low doses used in the treatment of enuresis and hyperactivity,
TCAs have relatively few side effects. With high doses, however, common
side effects include dry mouth, headache, sedation and malaise. There
is also a risk of cardiac arrhythmias and sudden death, especially with
desimipramine. To reduce this risk, an ECG should be carried out before
embarking on anything more than low-dose treatment, in order to check