|
|
Website sponsored by
an unrestricted educational grant |
 |
|
|
ANTIDEPRESSANTS IN CHILDREN AND ADOLESCENTS
SCIENTIFICALLY CONSIDERED
DR L SCRIBANTE
Dr Scribante is currently a consultant in the Department of Psychiatry,
University of Pretoria, at the Weskoppies Hospital in the Child
and Adolescent Unit.
This is a lecture that was given by Dr Scribante at the Weskoppies
Hospital on the 08 April 2005 and the Denmar Private Psychiatric
Clinic in Pretoria on the 26 July 2005.
Hopefully this will help clarify the current position on the use
of antidepressants in children and adolescents.
CONTENTS
- Introduction
- Basic science of psychopharmacology in a paediatric population
- i) Pharmacokinetic Principles
- ii) Pharmacodynamic Principles
- Specific Antidepressant Groups and drugs
- i) The Serotonin Re-uptake Inhibitors
- (a) Fluoxetine
- (b) Sertraline
- (c) Fluvoxamine
- (d) Paroxetine
- (e) Citalopram
- (f) Escitalopram
- ii) The Tricyclic Antidepressants
- iii) The Serotonin-Noradrenaline Re-uptake Inhibitors
- (a) Venlafaxine
- (b) Duloxetine
- iv) Other Antidepressants
- (a) Bupropion
- (b) Nefazodone
- (c) Mirtazapine
- (d) Moclobemide
- Trends in Antidepressant use in the USA from 1998—2002
- Conclusion
- References
Antidepressants in Children and Adolescents Scientifically Considered
Depressive disorders are a leading cause of morbidity and mortality
in the paediatric age group . Mood disorders also remain the strongest
predictor of suicide risk in adolescents and the earlier the onset
of the mood disorder, the greater the relative risk. However, despite
this fact, the use of psychiatric medication for children has always
been a controversial issue and the recent spate of reports on an
association between the use of antidepressants and adolescent suicide
, , , sparked the debate around the use of antidepressants in children
and adolescents once again.
As should always be the case in medicine, we as clinicians and scientists
need to look at the scientific evidence for and against the use
of antidepressants in children and adolescents. Paediatric psychopharmacology
has entered a new era with more research being done than ever before.
Although this is a positive change, it leaves one with the dilemma
of how to interpret the available data, keeping in mind that negative
findings may not be reported .
This paper will review the current evidence and scientific knowledge
in order to help the reader come to his/her own conclusions on the
use these medications in a paediatric population. This paper will
look at all the indications for the use of antidepressants and not
only at their use in depressive disorders.
Basic science of psychopharmacology in a paediatric population
- Pharmacokinetic Principles
The data pertaining to children and adolescents specifically is
scarce; therefore dosage recommendations are often extrapolated
from adult data. This can obviously lead to some errors in dosing.
Clinical observation suggests that children and adolescents need
larger weight-adjusted doses of most medications than do adults
to achieve comparable blood levels and therapeutic effect. This
is due to the shortened half-life, of medication in general due
to of an increased rate of metabolism and elimination found in children
when compared to adults. When prescribing antidepressants to children
or adolescents, one should always start with low doses and increase
the dose slowly to avoid side effects and to allow for pharmacokinetic
differences , .
The important factors that influence the bio-availability of medication
are absorption, distribution, metabolism and excretion.
Absorption
The route of admission and the first pass effect of the hepatic
system mainly influence absorption of medication.
The following theoretical concerns have been raised:
- The stomach content of children is less acidic than that
of adults. This could theoretically slow the absorption of weakly
acidic drugs such as anticonvulsants, antidepressants and amphetamine.
- Children have fewer and less diverse intestinal flora than
adults. This could theoretically lessen the absorption of phenothiazines,
which can lead to very high doses being necessary to obtain
a therapeutic effect.
It is unclear how much of an influence the above differences have
on actual blood levels found in children and adolescents.
Distribution
The distribution of any medication through the body is influenced
mainly by the water and fat distribution of the individual. Distribution
is also influenced by cardiac output, regional blood flow, organ
perfusion pressure, permeability of cell membranes, acid-base balance
and binding to proteins. Each of these factors change during development.
- The proportion of body fat is highest at birth and decreases
towards puberty, after which it increases again. Children have
proportionally less body fat than do adults. One would thus
expect higher concentrations of lipophilic drugs in children.
In actual fact, the blood concentration of lipophilic drugs
is lower in children than in adults due to other mechanisms
(e.g. faster metabolism) influencing the kinetics.
- The relative volume of extracellular water is higher in
children than it is in adults. In the newborn full term infant,
the extracellular water comprises 40- 50% of the baby's weight.
By the age of 10 to 15 years this percentage has decreased to
15 — 20% of weight. This leads to lower serum concentrations
of hydrophilic drugs, like Lithium, in smaller children.
- Although protein binding of drugs may be reduced in young
children, this does not seem to affect distribution of medication.
- The blood brain barrier is more permeable in children than
it is in adults. This affects only the concentration of unbound
drugs, such as Lithium, in the cerebro-spinal fluid. (Protein-bound
drug also crosses the blood brain barrier in children, thus
keeping the equilibrium between available and bound drug stable.)
Metabolism
Most drugs are lipid soluble, which is necessary for absorption,
distribution and availability at receptor sites. These drugs need
to be metabolised in the liver in order to be effectively eliminated.
Phase 1 reactions, catalysed by hepatic microsomal enzymes (the
cytochrome P450 system), are needed to convert drugs to forms more
suitable for excretion. During phase 2 reactions conjugation takes
place to facilitate excretion. Certain drugs, such as 3- hydroxybenzodiazepines
(e.g. lorasepam and oxasepam) and lamotrigine undergo only phase
2 reactions and are thus cleared as long as there is good renal
function, regardless of hepatic function.
The relatively high doses of psychotropic medication needed in a
paediatric population are most commonly explained by increased hepatic
metabolic capacity. Although cytochrome enzymes come “on-line” at
different developmental stages, they are more active when in the
latent phase and thus metabolise more effectively. Their activity
declines to adult levels after puberty. Thus for CYP metabolised
drugs, children need a higher mg/kg dose than do their adult counterparts
to achieve steady-state plasma levels.
Most psychotropic drugs are metabolised by this system. Some drugs
are metabolised by more than one enzyme, for example Sertraline
is N-demethylated by six different pathways. Clomipramine is demethylated
by three enzymes to an active metabolite (Desipramine); this metabolite
is, in its turn, hydroxilated by a different enzyme to an inactive
form.
Genetic differences in CYP enzymes also influence metabolic rate.
Theses differences will not be considered in detail here, as they
are not specific to the paediatric population.
- CYP45O inducers and inhibitors
Inhibition of the CYP system leads to increased blood levels of
certain drugs and induction of the system leads to decreased blood
levels. Induction takes some time (3 to 10 days) to develop and
to terminate (5 to 12 days) once the drug is not administered any
more. Tables are available in textbooks of psychiatry and pharmacology
listing enzyme inhibitors and inducers. The following table lists
only the antidepressant medications that influence the CYP system
and that are substrates for it. For full information on other drugs,
please refer to standard textbooks on psychiatry.
| |
CYP 1A2 |
CYP 2C9 |
CYP 2C19 |
CYP SD6 |
CYP 3A |
| INHIBITORS |
Fluvoxamine |
Fluoxetine |
Citalopram |
Amitriptyline |
Fluoxetine |
| |
|
Fluvoxamine |
Fluoxetine |
Citalopram |
Fluvoxamine |
| |
|
Sertraline |
Fluvoxamine |
Clomipramine |
|
| |
|
|
|
Desipramine |
|
| |
|
|
|
Fluoxetine |
|
| |
|
|
|
Imipramine |
|
| |
|
|
|
Nortriptyline |
|
| |
|
|
|
Paroxetine |
|
| |
|
|
|
Sertraline |
|
| |
|
|
|
|
|
| INDUCERS |
St John's Wort |
|
|
|
St John's Wort |
| |
|
|
|
|
|
| SUBSTRATES |
Amitriptyline |
Amitriptyline |
Amitriptyline |
Amitriptyline |
Amitriptyline |
| |
Clomipramine |
Fluoxetine |
Citalopram |
Citalopram |
Citalopram |
| |
Fluvoxamine |
Sertraline |
Clomipramine |
Clomipramine |
Clomipramine |
| |
|
|
Imipramine |
Desipramine |
Fluoxetine |
| |
|
|
Sertraline |
Fluoxetine |
Imipramine |
| |
|
|
Venlafaxine |
Fluvoxamine |
Mirtazapine |
| |
|
|
|
Hydroxibupropion |
Reboxetine |
| |
|
|
|
Imipramine |
Sertraline |
| |
|
|
|
Maprotiline |
Trazodone |
| |
|
|
|
Mirtazapine |
|
| |
|
|
|
Nortriptyline |
|
| |
|
|
|
Paroxetine |
|
| |
|
|
|
Reboxetine |
|
| |
|
|
|
Sertraline |
|
| |
|
|
|
Venlafaxine |
|
It is important to remember that non-psychiatric drugs can also
influence the metabolism of psychotropic medication and they can
be influenced by effects caused by psychotropic medications.
Excretion
Renal function in infants and children approximates that of adults.
Developmental changes in renal function therefore do not contribute
significantly to age-related differences in drug disposition.
- Pharmacodynamic Principles
Three aspects of human brain function are critical to understanding
psychopharmacology. These are the neuronal circuitry, synaptic neurotransmission
and intracellular information processing.
Neuronal circuitry
- The thalamus is the gateway to cortical processing of all
incoming sensory information.
- The association cortex integrates the information from different
areas in the brain.
- The medial temporal lobe has two major functions, namely
integration of multimodal sensory information and attaching
limbic valence to sensory information.
- The basal ganglia modulate cortical activity via a cortico-striato-pallido-thalamo-cortical
loop.
All the projections in this basic circuitry are glutaminergic, except
for the projections from the basal ganglia to the thalamus that
are GABAergic. The glutaminergic neurons are under inhibitory control
of the GABA neurones.
In addition there are cholinergic neurons projecting to the basal
forebrain and brain stem, dopaminergic neurons in the substantia
nigra and ventral tegmental area, noradrenergic neurons in the locus
ceruleus and serotonergic neurons in the raphe nuclei.
Neurotransmitter systems
Serotonin, Norepinephrine and Dopamine have all been considered
as playing a possible role in the development of depression.
1. Serotonergic Neurotransmission
Most serotonergic cells overlap with the brainstem raphe nuclei.
A rostral group projects to the thalamus, hypothalamus, amygdala,
striatum and cortex. The two remaining groups project to other brainstem
neurons, the cerebellum and the spinal cord.
Modulation of serotonergic receptors and the presynaptic re-uptake
site for serotonin is beneficial in the treatment of anxiety, depression,
obsessive-compulsive disorder and schizophrenia.
2. Noradrenergic Neurotransmission
About half of the noradrenergic neurons are located in the locus
ceruleus and they project to the cortex, hippocampus, thalamus,
cerebellum and spinal cord. The primary function of the locus ceruleus
is to determine whether attention should be focused on the external
environment or should be monitoring the body's internal milieu.
The other noradrenergic neurons are found in the tegmental region
from where they innervate the hypothalamus, basal forebrain and
spinal cord.
Noradrenergic projections modulate sleep cycles, appetite, mood
and cognition.
Specific antidepressant groups and drugs
In spite of the fact that specific data about effectiveness of antidepressant
medication in paediatric age group is limited, these drugs are widely
prescribed to children and adolescents. This is due to the fact
that depression is a serious condition and treatment cannot necessarily
wait for definitive scientific support.
1. The Serotonin Re-uptake Inhibitors
These antidepressants are considered first line treatment for children
and adolescents suffering from major depressive disorder . They
have also proved to be the most effective psychopharmacological
agents to address OCD in children and adolescents, although the
studies done were small and the magnitude of response found to SSRI
was not big. The currently available SSRI's are Fluoxetine, Citalopram,
Escitalopram, Sertraline, Paroxetine and fluvoxamine. This paper
will firstly consider SSRI's as a group and then look at the available
evidence for each individual drug.
There is no evidence regarding duration of treatment for children
and adolescents specifically. Based on adult studies, treatment
for major depressive disorder should be at least one year. There
is no evidence to suppose that this should be different in children
and adolescents.
- Mechanism of action
The SSRI's block the serotonin transporters located on the pre-synaptic
nerve terminal. Over time, this blockade leads to desensitisation
of auto receptors for serotonin. The desensitised auto receptors
do not exhibit their usual inhibitory effect on serotonin release,
leading to an increase in available serotonin. Based on animal
studies, the main location for this in depression appears to
be the hippocampus and in OCD the orbital frontal cortex.
- Pharmacokinetics
All SSRI's have long half-lives permitting once daily dosing.
Paroxetine is metabolised quicker in children than in adults,
but the recommendation is still for once daily dosing.
- Empiric support for use in peadiatric populations
Monotherapy is simple with the use of SSRI's. Published trials
(see later for detail and references) looking at the use of
SSRI's in OCD, major depressive disorder and anxiety disorders
reported superiority for SSRI's to placebo in children and adolescents
for all of these diseases.
- FDA approval
Fluoxetine has been approved by the FDA for use in paediatric
Obsessive- Compulsive Disorder (OCD) for children 6 years and
older and Fluvoxamine for children 8 years and older with OCD.
The FDA has given no other approval for the use of SSRI's in
children.
- Side-effects
As a group the SSRI's are well tolerated and potentially serious
side effects have not been reported. Common side effects seen
in children and adolescents are gastro-intestinal side effects
and behavioural activation; Signs of behavioural activation
include motor restlessness, insomnia, impulsive and/or disinhibited
behaviour. The behavioural activation is usually seen in the
beginning of treatment and with dose increases. Sexual side
effects can also occur.
Fluoxetine
This is the SSRI most studied in the paediatric age group. Both
open label and placebo-controlled studies have shown superior efficacy
to placebo in the treatment of children and adolescents with major
depressive disorder. The usual starting dose for school-age children
with depressive disorder is 5 to 10 mg daily, with dose increases
every week to two weeks. The usual dose range is 5 to 40mg daily.
Fluoxetine was studied for the use in adolescents aged 12 to 17
years with major depressive disorder during a 12 week randomised
controlled trial comparing Fluoxetine alone, CBT alone, Fluoxetine
plus CBT or pacebo. 439 patients were enrolled in this study. Fluoxetine
plus CBT was found to be the superior of these treatments, with
Fluoxetine alone a superior treatment to CBT alone. The dose range
of Fluoxetine used ranged from 10 to 40 mg daily .
Fluoxetine has also been tested in three placebo controlled studies
for use children and adolescents. These studies provide support
for the efficacy of Fluoxetine in the use for paediatric OCD.
Sertraline
Sertraline has been studied in two open label studies and for use
in paediatric depression. This led to two further placebo-controlled
double-blind trials .
These studies had a combined total of 153 patients from the ages
of 6 to 17 years enrolled. Patients received dosages from 50 to
200 mg Sertraline daily for 10 weeks. The studies showed Sertraline
to be effective and well tolerated when compared to placebo.
Sertraline has also been tested in children who suffer from OCD.
97 patients received 12 weeks of treatment of either Sertraline
alone, Sertraline plus CBT, CBT alone or pill placebo. CBT plus
Sertraline proved to be superior to all other treatment modalities
with Sertraline alone and CBT alone being equally effective and
both superior to pill placebo . Sertraline has also been tested
against placebo alone with efficacy shown for Sertraline.
The usual daily dose for Sertraline in children and adolescents
is 50 to 150mg daily in once a day doses.
Fluvoxamine
In two studies with a total of 257 children and adolescents diagnosed
with OCD, Fluvoxamine showed efficacy above placebo and this effect
was sustained during open label follow-up .
Fluvoxamine showed efficacy when compared to placebo in the treatment
of generalised anxiety disorder, social phobia and separation anxiety
in a study of 128 children aged between 6 and 17 years.
The daily starting dose for Fluvoxamine was 25mg daily with an increase
to 25mg twice daily in the first week. After this the dose was increased
by 25mg daily every week as tolerated by the patient. The usual
daily dose is 50 to 200mg daily.
Paroxetine
On 10 June 2003 the United Kingdom Department of Health issued a
press release prohibiting the use of Paroxetine for depression in
patients younger than 18 years. On 19 June 2003 the FDA issued a
recommendation that Paroxetine not be used in the treatment of major
depressive disorder in children and adolescents .
Paroxetine has been studied for use in major depressive disorder
in an open label trial and in comparison with Imipramine and placebo
in a recent placebo-controlled multi center trial. Paroxetine showed
superiority to both Imipramine and placebo .
Paroxetine was studied in two placebo controlled studies looking
at treatment of paediatric OCD. Both studies showed efficacy above
placebo.
Paroxetine has also been tested in children and adolescents with
Panic disorder (18 patients) with social anxiety disorder (319 patients)
and dysthymia (7 patients) Paroxetine was found to be effective
in all of these studies.
The starting dose for Paroxetine in children is 5 to 10mg daily
with a usual dose range of 10 to 40mg daily.
Citalopram
Citalopram was recently studied in a double-blind placebo controlled
study in children diagnosed with major depressive disorder . Children
and adolescents suffering from major depressive disorder were enrolled.
A total of 174 patients were recruited and 138 patients completed
the study. Citalopram was administered at dosages of 20 or 40 mg
daily. Citalopram was shown to be statistically significantly more
effective than placebo in the treatment of depression and was well
tolerated.
Citalopram was tested in an open label study in 23 patients suffering
from paediatric OCD . Although the results are not significant,
50% of patients showed a clinically meaningful response. In a 12
week open label study of Citalopram in 8 adolescents suffering from
PTSD , all adolescents showed statistically significant improvement
of PTSD symptoms. However, they failed to show improvement in self-reported
depressive symptoms.
Lepola et al reported on three case studies using Citalopram for
patients diagnosed with early-onset panic disorder or school phobia
to good effect .
Escitalopram
To date one open-label study of Escitalopram in children and adolescents
with major depression has been undertaken . 12 patients were enrolled
and Escitalopram was shown to lead to improvement in depressive
symptoms and was also found to be well tolerated. The mean dose
used was 10 to 20mg daily.
Escitalopram has also been tested in a pilot study for use in the
treatment of impulsive aggression . This study was very small with
only 9 patients finishing the trial. A marked improvement in impulsive
aggression was seen.
2. The Tricyclic Antidepressants
Tricyclic antidepressants have been used to treat psychiatric disorders
in children for at least three decades. They have been used to treat
depressive disorders, separation anxiety disorder and enuresis.
Their use has, however, become less popular as newer medication
became available. Despite losing popularity as first line drugs
in the treatment of depressive disorders, the TCA's are still seen
as second line drugs in the treatment of depressive disorders.
Desipramine is used for the treatment of ADHD and Clomipramine is
used for the treatment of OCD in children. Clomipramine is especially
useful in children with autism and OCD-like symptoms. Imipramine
is used in the treatment of enuresis.
- Mechanism of action
The TCA's are multipotent re-uptake inhibitors. They inhibit
the presynaptic re-uptake of both norepinephrine and serotonin.
Desipramine is the most selective in its ability to block the
re-uptake of norepinephrine and Clomipramine is the most potent
inhibitor of serotonin re-uptake. This leads to their relative
effectiveness in the treatment of ADHD and OCD respectively.
- Pharmacokinetics
Therapeutic levels for TCA's are not well established in the
paediatric population, since serum levels vary widely in individuals
taking the same oral dose. This variation can be attributed
to genetic differences in GYP 450 activity. The half-life of
TCA's is generally long enough to allow for once or twice daily
dosing.
- Empiric support for use in paediatric populations
The TCA's have failed to show superiority to placebo in the
treatment of depressive disorders. The support for use of TCA's
in non-OCD anxiety is also equivocal, with some studies showing
efficacy, but others not. Desipramine has showed efficacy in
ADHD in two studies and Clomipramine for the treatment of OGD.
Imipramine has been showed to be effective in the treatment
of nocturnal enuresis in more than 40 double- blind trials.
- FDA approval
Clomipramine has been approved for use in children 10 years
and older with OCD.
No other FDA approval has been given to the use of TCA's in
paediatric populations, in spite of the fact that more than
40 double-blind studies have shown the efficacy of Imipramine
in the use for enuresis.
- Side-effects
The unfavourable side-effect profile of the TCA's combined with
the relative lack of proof of efficacy has led to lesser use
of TCA's in paediatric populations.
There is a whole range of side effects attributable to the TCA's.
The most ominous side effect related to TCA's is sudden death due
to tachyarrythmias. The following precautions are recommended if
TCA's are used in paediatric populations:
- Stepwise dosing within clear weight adjusted margins;
- Careful ECG monitoring;
- Full disclosure of risk : benefit ratio in the planning
process; and
- Use as second-line medications
Other side effects which cause problems include sedation, dizziness,
dry mouth, excessive sweating, weight gain, urinary retention, tremor
and agitation. Lowering the dose, changing the dosing schedule and
switching between groups of TCA's are all ways of managing the side
effects,
Clomipramine has been tested in four studies of paediatric OCD against
placebo and in one against Desipramine. Clomipramine was found to
be superior to placebo and in a meta-analysis of studies of paediatric
OCD was found to be superior in treatment of OCD symptoms to SSRI.
3. The Serotonin-Noradrenaline Reuptake Inhibitors
Venlafaxine is a serotonin re-uptake inhibitor at lower doses (<150mg/day)
and a sertonin-noradrenalin reuptake inhibitor at higher doses.
Duloxetine is an inhibitor of reuptake for both at all dosages.
- FDA approval
Neither Venlafaxine nor Duloxetine have FDA approval for use
in children or adolescents.
- Venlafaxine
One placebo-controlled study of Venlafaxine in children has
been done. This study enrolled 32 patients and failed to show
efficacy for Venlafaxine in the treatment of paediatric depression.
This result could have been the result of the small sample size
and Venlafaxine warrants further study in paediatric populations.
- Duloxetine
To date, no studies have been done with Duloxetine in paediatric
age groups.
4. Other antidepressants
- · FDA approval
No FDA approval has been given for any other antidepressant
in children or adolescents.
Bupropion Bupropion was only approved for use in depression
for adults in March 2005 in South Africa.
The mechanism of action of Bupropion is unclear, but it appears
to have both dopaminergic and noradrenergic effects.
No studies have been done on the use of Bupropion in paediatric
depression. One study involving 72 children diagnosed with ADHD
showed efficacy above placebo, but the effect size was smaller than
that seen for stimulants. In a more recent study involving 24 adolescents
diagnosed with co-morbid ADHD and depression 58% showed improvement
of both conditions with sustained release Bupropion.
Dosages used for children with ADHD varied from 50 to 200 mg daily
in divided doses (3 to 6 mg/kg/day).
Side effects seen with Bupropion include agitation, insomnia, skin
rashes, nausea, vomiting, constipation and tremor. Bupropion may
also reduce the seizure-threshold in a dose dependant manner, therefore
total daily dose should not exceed 300 mg daily in children and
individual doses should not exceed 150mg per dose.
Nefazodone
Nefazodone is a potent SHT2a antagonist in the postsynaptic membrane
as well as a moderate serotonin and norepinephrine reuptake inhibitor.
A study involving 28 children and adolescents was undertaken looking
at the pharmacokinetic profile and efficacy of Nefazodone. The positive
results of this study have led to a placebo-controlled trial in
children aged 12 to 18 years. The results of this study are not
yet available.
Mirtazapine
Mirtazapine is a specific serotonergic antidepressant that enhances
both serotonergic and noradrenergic neurotransmission. Adult patients
using Mirtazapine show rapid improvement in anxiety and agitation.
An open label trial in adolescent patients (aged 12 to 18 years)
was conducted in Finland. 23 patients finished the 12 week study
period. A significant improvement in most adolescents was reported,
with anxiety symptoms also showing improvement. Mirtazapine was
well tolerated. The dose range of Mirtazapine used was 30 to 45
mg daily.
Moclobemide
A double-blind 5 weeks long study was done in young adolescents
in 1998. This study found Moclobemide to be effective, tolerable
and safe as reported by Haapasalo-Pesu et al.
Trends in antidepressant use in the USA from 1998 to 2002 ,
Delate et al did a study looking at ambulatory prescription claim
data for more than 1,9million life-years of commercially insured
children under the age of 18 for the years 1998 to 2002, inclusive.
They found that the overall prevalence of antidepressant use among
children increased from 160 per 10 000 (1,6%) in 1998 to 240 per
10 000 (2,4%). The group of children most likely to use antidepressant
medication in 2002 was girls aged 15 to 18 years (6,4% of girls).
This increase in antidepressant use can mostly be attributed to
greater use of selective serotonin reuptake inhibitors.
Conclusion
It is clear that there is still much work to be done in the field
of paediatric psychopharmacology. This holds true not only for antidepressant
medication, but for other medications as well.
In the interim it is left to us to make the best clinical decisions
we can make with the information available to us.
I would like to quote the words of PR Mansfield, .
“It is common to assume that most new drugs are superior, but only
about 3% of new drugs offer real advances. It is normal to use shortcuts
when faced with inadequate time, skills, or resources to examine
the evidence fully, or when the evidence required is not available.
Some common shortcuts are listed below:
Newer is better.
Experts know best.
If there is a mechanism for how it works, it works.
If my peers are using a therapy, so should I.
If the manufacturers give gifts, I should support them in return.
If I see changes after prescribing a therapy, that therapy must
be the cause.”
References
- Emslie,GJ, Mayes TL and Hughes CW. Update in the Pharmacologic
Treatment of Childhood Depression. The Psych Clinics North Am
23(4) Dec 2000: 813—35
- Statement from the American Academy of Child and Adolescent
Psychiatry for the Food and Drug Administration Joint Meeting
of the Psychopharmacological Drugs Advisory Committee and the
Pediatric Subcommittee of the Anti-Infective Drugs Advisory
Committee on Child and Adolescent Suicidality and Anti-Depressant
Drugs. February 2, 2004
- Culpepper L, Davidson JRT et al. Suicidahty as a Possible
Side Effect of Antidepressant Treatment. J Clin Psych 65(6);
June 2004: 742 — 9
- Jick H, Kaye JA and Jick SS. Antidepressants and the Risk
of Suicidal Behaviors. JAMA 292(3); July 21 2004: 338 —43
- Olfson M, Shaffer D et al. Relationship between Antidepressant
Medication Treatment and Suicide in Adolescents. Arch Gen Psych
60; October 2003: 978 — 82
- Geller DA, Biederman J et al. Which SSRI? A Meta-Analysis
of Pharmacotherapy Trials in Pediatric Obsessive-Compulsive
Disorder. Am J Psych 160(11); November2003: 1919— 28
- Child and Adolescent Psychiatry — A Comprehensive Textbook.
Editor M Lewis. Lippincott Williams and Wilkins. Chapter 76:
Pediatric Psychopharmacology I: Pharmacokinetic and Pharmacodynamic
Principles. Pg 939 — 50.
- Child and Adolescent Psychiatry A Comprehensive Textbook.
Editor M Lewis. Lippincott Williams and Wilkins. Chapter 77:
Pediatric Psychopharmacology II: General Principles, Specific
Drug Treatments and Clinical Practice. Pg 962—6
- Pediatric Psychopharmacology. Editors A Martin, L Scahill
et al. Oxford University Press. Chapter36: Depressive disorders.
Pg 466 — 83
- Essential Psychopharmacology. Stephen M Stahl 2 Edition
Cambridge University Press. Chapters 5, 6 and 7
- Hughes C, Emslie GJ et al. The Texas Children's Medication
Algorithm Project: Report of the Texas Consensus Conference
Panel on Medication Treatment of Childhood Major Depressive
Disorder. J Am Acad Child Adol Psych; 38(11) November 1999:
1442-54
- March JS et al. Fluoxetine, Cognitive-Behavioral Therapy
and Their Combination for Adolescents with Depression. JAMA
292(7); 18 August 2004: 807 — 20
- Wagner KD, Ambrosini P et al. Efficacy of Sertraline in
the Treatment of Children and Adolescents with Major Depressive
Disorder. Two Randomised Controlled Trials. JAMA 290(8); 27
August 2003: 1033 — 41
- March JS et al. Cognitive-Behavior Therapy, Sertraline,
and their Combination for Children and Adolescents with Obsessive-Compulsive
Disorder. JAMA292(16); 27 October2004: 1969—76
- Riddle MA, Reeve E et al. Fluvoxamine for Children and Adolescents
with Obsessive-Compulsive Disorder: A Randomised, Controlled,
Multicenter Trial. J Am Acad Child Adolesc Psych 40(2); February
2001: 222 - 9
- Riddle, M. Paroxetine and the FDA (Letters to the Editor).
J Am Acad Child Adol Psych 43(2) February 2004: 128—30
- Rey-Sanchez F, Gutierrez-CasaresJR. Paroxetine in Children
with Major Depressive Disorder: An Open trial. J Am Acad Child
Adol Psych 36(10) October 1997: 1443—7
- Masi G, Toni C et al. Paroxetine in child and Adolescent
Outpatients with Panic Disorder. J Child Adolesc Psychopharm;
11(2) 2 November 2001: 151 —7
- Wagner KD, Berard R et al. A Multicenter, Randomized, Double-blind,
Placebo-Controlled Trial of Paroxetine in Children and Adolescents
With Social Anxiety Disorder. Arch Gen Psychiatry 61; November2004:
1153— 62
- Nobile M, Bellotti B et al. An Open Trial of Paroxetine
in the Treatment of Children and Adolescents Diagnosed with
Dysthymia. J Child Adol Psychopharmacol 10(2); October 2000:
103—9
- Wagner KD, Robb AS et al. A Randomized, Placebo-Controlled
Trial of Citalopram for the Treatment of Major Depression in
Children and Adolescents. Am J Psych 161(6); June 2004: 1079—83
- Thomsen PH. Child and Adolescent Obsessive-Compulsive Disorder
Treated with Citalopram: Findings from an Open Trial of 23 Case&
J Child Adolesc Psychopharmacol 7(3); March 1997: 157—66
- Seedat S, Lockhat R et al. An open trial of Citalopram in
adolescents with post-traumatic stress disorder. lnt Clin Psychopharmacol
16(1); 21 —5
- Lepola U, Leinonen E. Koponen H. Citalopram in the Treatment
of Early- Onset Panic Disorder and Social Phobia. Pharmacopsychiatry
29(1); January1996: 30—32
- Wagner KD, Saikali K. Open-Label Evaluation of the Safety
and Efficacy of Escitalopram in Children and Adolescents with
Major Depression. Presentation at the 157 annual meeting of
the American Psychiatric Association May 1 — 6, 2004.
- Armenteros JL, Lewis J et al. A Pilot study of Escitalopram
in the Treatment of Impulsive Aggression. Poster presetation
June 2004.
- Child and Adolescent Psychiatry — A Comprehensive Textbook.
Editor M Lewis. Lippincott Williams and Wilkins. Chapter 56
Modern Approaches to Enuresis and Enkopresis. Pg 702 —3
- Haapasalo-Pesu K, Vuola T et al. Mirtazapine in the treatment
of Adolescents with Major Depression: An Open-Label, Multicenter
Pilot Study. J Child Adol Psychopharmacol 14(2); February 2004:
175—84
- Child and Adolescent Psychiatry — A Comprehensive Textbook.
Editor M Lewis. Lippincott Williams and Wilkins. Chapter 52.
Attention Deficit Hyperactivity Disorder Pg 660
- Delate I, Gelenberg AJ et al. Trends in the Use of Antidepressants
in a National Sample of Commercially Insured Pediatric Patients,
1998 to 2002. Psychiatric Services 55(4); April 2004: 387 —
91
- Mansfield PR. Healthy scepticism's new ad watch: understanding
drug promotion. Med J Australia. 179; 2003: 644 - 5
|
|
|
