Child psychiatric disorders: paradigm shift of management

Introduction

Children and adolescents suffer from all the illness of adulthood.[Taylor et al. 2009] It is common for psychiatric illness to commence more diffusely, present atypically and respond less predictably.[Taylor et al. 2009] Childhood onset illness is likely to be at least as severe and functionally disabling as adult onset illness.[Taylor et al. 2009] A variety of interventions are available to help children and adolescents with psychiatric illness.[Sexson 2005] It is essential to base treatment interventions on a comprehensive understanding of the child’s and family’s problems and strength so that a multidimensional plan can be developed.[Sexson 2005] Psychotropic medication in children and adolescents is a matter of concern worldwide. Very few psychotropic drugs are licensed for use in children.[Taylor et al. 2009] There are few randomised controlled trials evaluating pharmacological treatments in children and adolescents for psychiatric disorder. However, in last decade there is a shift in the paradigm and the off label use of psychotropic drugs in this particular age group has increased to a great extent. The safe and effective use of medications in this group has enabled many children to attend school and achieve academic success.

Why this concern

Safety and efficacy of most psychotropic drugs are based on clinical experience than on evidence from large clinical trial data. In most of the diseases except attention deficit hyperkinetic disorder (ADHD) and obsessive compulsive disorder (OCD), results from adult studies are extrapolated. Also developmental differences in pharmacokinetics and pharmacodynamics result in unexpected outcome.

Pharmacological differences

There are mainly pharmacokinetic differences between children and adolescents and the adult group which governs some of the rule while prescribing medications to this special population. These are as follows:

a) As compared to adults this group has lower volume of distribution and so low dose is required.

b) On the other hand, they have faster rate of metabolism as compared to adults.

c) So calculation of dose is difficult and should be individualised. The clinician should also be prepared to prescribe higher mg per kg body weight as compared to adults.

Principles of prescribing practice in childhood and adolescent[Nunn and Dey 2003]

• 1. Target symptoms not diagnoses: Treatment in children and adolescents should target key symptoms as diagnosis is difficult to make. Also due to presence of associated comorbidity accurate diagnosis becomes difficult to establish.

  2. Start low, go slow but prepare to end with more: In prescribing we should follow the golden rule of start low and go slow, but at times due to faster rate of metabolism requires greater mg/ kg per day as compared to adults.

  3. Multiple medications often required: In childhood onset illness multiple medications are often required as they usually present with more severe illness.

  4. Allow time for an adequate trial of treatment: children often require longer periods of treatment before responding as they are generally more ill than their adult counterparts. So an adequate trial of at least eight weeks is required for diseases like depression or schizophrenia.

  5. Monitor outcome in more than one setting: The response should be monitored in different settings (e.g. home, school) and dose should be titrated so that they can be benefited without much difficulty.

  6. Patient and family medication education is essential.

Works to be done before starting medications[Sexson 2005]

• 1. The child’s parents or family should be engaged.

  2. They should be psycho educated about the diagnosis or the problem of the patient.

  3. They should be informed about the treatment options.

  4. Information about the medications should be given to the care takers -- what it is expected to do, what it cannot do, duration of medication treatment, side effects and how to manage them.

  5. Informed consent should be taken before starting medication therapy.

Psychopharmacology in different disorders of children and adolescents and the important guidelines

Depression

The National Institute of Health and Clinical Excellence (NICE) recommend a stepped model of care for the management of depressive disorder in children and adolescents. Introduction of medication is recommended only when there is failure to respond to psychological therapy or if the depression is more severe. Fluoxetine[National Institute for Clinical Excellence 2005, Whittington et al. 2004, Medicines and Healthcare Products Regulatory Agency 2003, Kratochvil et al. 2006, Tsapakis et al. 2008] is the medication of choice. NICE recommends its use only in combination of psychological forms of therapy.[March et al. 2004] Fluoxetine should be administered starting with a low dose of 10 mg/day. It has been suggested that fluoxetine with its long duration of action may have advantages in relation to poor adolescent compliance. Regarding duration of treatment adult guidelines are usually followed. They should be taken for six to nine months after recovery from a single episode. In those patients who have had multiple episodes, there is evidence of benefit from maintenance treatment for at least two years. If there is no response to fluoxetine an alternative selective serotonin reuptake inhibitor (SSRI) may be used cautiously by specialists. The two SSRIs recommended by NICE other than fluoxetine are sertraline and citalopram. There are no clear guidelines for management of treatment resistant depression in adolescents. Evidence suggests that adolescents who failed to respond to adequate treatment with a SSRI showed a higher rate of clinical response when switched to another SSRI or venlafaxine. Tricyclic antidepressants (TCAs) are not effective in pre pubertal children but may have marginal efficacy in adolescents. NICE advice against the use of TCA in this group given the high risk to benefit ratio. Omega 3 fatty acids may be effective in childhood depression but evidence is minimal.

American Academy of Child and Adolescent Psychiatry recommends the use of pharmacotherapy in children and adolescents with (a) moderate to severe depression, (b) chronic or recurrent depression, (c) suicidality, (d) agitation and psychosis. Treatment with antidepressant may be administered alone until the child is amenable to psychotherapy or if appropriate they can be combined with psychotherapy from the beginning of treatment. Also depressed youth who do not respond to monotherapy treatment -- either psychotherapy or antidepressants -- require a combination of these two treatment modalities. Fluoxetine is the only medication to be approved by the US Food and Drug Administration (FDA) for the treatment of child and adolescent depression. FDA also asks to keep a close monitor on the suicidality during the treatment process. FDA recommends that depressed youths should be seen every week for the first four weeks and bi weekly thereafter. Those with a family history of bipolar disorder should be carefully monitored for onset of mania or mixed state. After the treatment with antidepressants is over, the discontinuation must be slow to avoid withdrawal symptoms. Treatment should be continued for at least six to 12 months.

Bipolar disorder

In this age group, bipolar affective disorder is often comorbid or shows symptom overlap with other child psychiatric disorders such as ADHD, conduct disorders and pervasive developmental disorders (PDDs).[ Baroni et al. 2009] The evidence base for treatment of bipolar disorder in youth is limited as compared to that for the adult disorders. Most trials are open label and there are only a few double blind placebo controlled trials. Also most evidence concerns adolescents, rather than children.

NICE recommends monotherapy and starting doses at the lower end to be primary pole in the treatment. Previous response, current medication, compliance, family and patient preferences will guide treatment decisions. Structural measurement of symptoms should be used routinely to evaluate progress and treatment outcome.

a. For presentation with psychosis or severe behavioural disturbance: Antipsychotic agent first line as compared to lithium.

b. In partial responders: Augment with a mood stabiliser.

c. Non responders: Alternative antipsychotic should be considered.

Medications approved by FDA

Antipsychotics: Risperidone is effective in reducing Young Mania Rating Scale (YMRS) scores either alone or in combination with lithium therapy. Risperidone is approved in the age group 10-17. Aripiprazole is recently approved by FDA in patients aged 10-17 years. Olanzapine is effective in treatment and well tolerated but is not approved by FDA.

Mood stabilisers: Lithium -- Open label trials show positive effects in acute treatment and maintenance. Lithium is approved by FDA for treatment of bipolar disorder in children and adolescent.

Other mood stabilizers -- Valproate, carbamazepine, lamotrigine can be used but are not approved by the FDA.

American Academy of Child and Adolescent Psychiatry states that, standard therapy based on the adult literature, typically includes lithium, valproate and/or atypical antipsychotic agents, with other adjunctive medications used as indicated.[Kowatch et al. 2005, Suppes et al. 2005]

The choice of medication should be made based on:

i. Evidence of efficacy

ii. The phase of illness

iii. Presence of confounding presentations (e.g. rapid cycling mood swings, psychotic symptoms)

iv. The agent’s side effect spectrum and safety

v. The patient’s history of medication response

vi. The preferences of the patient and his/her family

Treatment should begin with an agent that is approved by FDA for bipolar disorder in adults. Then, depending upon the response other agents may be used. For patients with clearly defined bipolar disorder, and comorbid ADHD, stimulant medications may be helpful for addressing ADHD symptoms once the patient’s mood symptoms are adequately controlled on a mood stabiliser regimen. Low dose mixed amphetamine salts is safe and effective for the treatment of comorbid ADHD once the child’s mood symptoms were stabilised with divalproex. Regarding the duration of the medication, current evidence suggests that the regimen needed to stabilise acute mania should be continued for 12 to 24 months. Maintenance therapy is often needed for youths with bipolar disorder, with some individuals needing lifelong therapy when the benefits of continued treatment outweigh the risks. This should be decided on a case by case basis after discussing the risks and benefits of continued treatment. Until more definitive information is available about the long term effects of mood stabilisers and antipsychotics, the clinician must balance the potential deleterious impact of symptom reoccurrence versus that of the side effects of the medications. Any attempts to discontinue prophylactic therapy should be done gradually, while closely monitoring the patient for relapse. Psychopharmacological intervention require baseline and follow up symptom, side effect and laboratory monitoring as indicated.

Anxiety in children and adolescents

Maudsley prescribing guidelines recommend that if anxiety is severe and disabling and cognitive behavioural therapy (CBT) is inappropriate or has failed, the use of medication should be considered. The combination of medication therapy and CBT is gold standard for anxiety in children and adolescents. Flouxetine is probably the drug of choice. Sertraline is also effective and safe molecule in this age group. Venlafaxine is also effective in children and adolescents.[March et al. 2007] Young people are more likely to develop disinhibition with benzodiazepines than are adults and care is required.

American Academy of Child and Adolescent Psychiatry recommends a multimodal treatment approach for children and adolescents with anxiety disorder. The treatment plan should consider education of the parents and the child about the anxiety disorder, consultation with school personnel and primary care physicians, CBT, psychodynamic psychotherapy, family therapy and pharmacotherapy, valid reasons for combining medication treatment with psychotherapy include the following -- need for acute symptom reduction in a moderately to severely anxious child, a comorbid disorder that requires concurrent treatment, and partial response to psychotherapy and potential for improved outcome with combined treatment. Imipramine is found to be efficacious along with CBT, in school refusing adolescents with severe anxiety and depression. SSRI have emerged as the medication of choice in the treatment of childhood anxiety disorders. The US FDA issued a black box warning and advised clinicians to carefully monitor paediatric patients receiving treatment with antidepressants for agitation and suicidality, particularly at the beginning of medication treatment or during dose changes.

OCD in children and adolescents

The treatment of OCD in children follows the same principles as in adults. Sertraline[March et al. 2006] (from age six years) and fluvoxamine (from age eight years) are the SSRIs licensed in the U.K. for the treatment of OCD in young people. Fluoxetine, fluvoxamine, paroxetine, citalopram and sertraline have all been shown to be effective and safe in young people with OCD. It is worth waiting for a response at a moderate therapeutic dose, rather than moving rapidly to high doses. If the SSRI is unsuccessful then a different SSRI should be tried or clomipramine may be used, but with caution. If there is comorbid depression along with OCD, then fluoxetine is the drug of choice. NICE recommends that if a young person has responded to medication, treatment should continue for at least six months after remission. For treatment refractory OCD in children, trials of clomipramine and/or augmentation with risperidone may be considered.

American Academy of Child and Adolescent Psychiatry recommends medication use for moderate to severe OCD along with CBT. Scores higher than 23 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Clinical Global Impression Severity Scale of marked to severe impairment provide a threshold for the consideration of drug intervention. SSRIs are the first choice of antidepressants. Though clomipramine is effective, it is not used as first choice due to potential side effects.

ADHD

The Maudsley guidelines suggest use of medications in the presence of impairment resulting from ADHD, in severe ADHD and also as a second line when psychological approaches have not been successful within a reasonable time or are inappropriate. Methylphenidate, dexamphetamne and atomoxetine are recommended within their licensed indications.

Methylphenidate is usually the first choice, but decision should include consideration of comorbid conditions (tics, Tourette’s disorder, epilepsy), tolerability and adverse effects, convenience of dosing, patient and/or parent preference. If using methylphenidate, modified release preparation should be considered due to tolerability and convenience. Dexamphetamine is an alternative central nervous system (CNS) stimulant. Atomoxetine is a suitable first line alternative to stimulants.[Weiss et al. 2005] Third line drugs include clonidine[Connor et al. 1999] and TCAs.[ Hazell 1996] There is some evidence to support the efficacy of carbamazepine[Silva et al. 1996] and bupropion. Modafinil appears to be effective but its safety is not established.[Biederman et al. 2006]

The following medications are approved by the U.S. FDA for the treatment of ADHD -- dextroamphetamine, methylphenidate, mixed salts amphetamine and atomoxetine.

Psychosis in children and adolescents

NICE recommends the same guidelines for treatment of psychotic disorders in children and adolescents as in adults except that metabolic adverse effects are more common and more intensive monitoring is required. First generation antipsychotics should generally be avoided in children. Clozapine seems to be effective in treatment resistant psychosis in adolescents, although this population may be more prone to neutropenia and seizures than adults.[ Kumra et al. 1998] American Academy of Child and Adolescent Psychiatry also suggests to use antipsychotics in the same way as in adults.

Autism spectrum disorders

The autism spectrum comprises of autism, Asperger’s syndrome and PDD not otherwise specified (PDD-NOS) and are categorised under PDD in ICD-10. Pharmacotherapies are commonly used in individuals with autism spectrum disorders (ASD) as adjuncts to psychological interventions. Currently, there is no single medication for ASD that alleviates symptoms in all three domains simultaneously. Targeting pharmacological intervention by identifying problem behaviours and the level of impairment caused by them is essential.

Pharmacological treatment of core symptom with ASD

Restricted repetitive behaviours and interests (RRBI) domain: SSRIs have become the most widely prescribed medication to treat RRBI in paediatric ASD populations. The evidence though is derived from single case studies and open label trials with only a few randomised controlled trials published to date.[Hollander et al. 2005] The SSRIs that have been studied include fluoxetine, fluvoxamine, sertraline, citalopram and escitalopram. The optimal dose required is less than that required to treat depression.[ Soorya et al. 2008] The mean dose of fluoxetine has been approximately 10 mg/day, starting from 2.5 mg. Other potential pharmacological treatments include second generation antipsychotics,[McDougle et al. 2005, Hollander et al. 2006] anticonvulsants and neuropeptide oxytocin.[Hollander et al. 2003] Research on risperidone indicates that it is effective in reducing repetitive behaviours in children who have high levels of irritability or aggression.

Social and communication impairment domain: Currently no drug has been consistently proven to improve the core social and communication impairments in ASD. Risperidone may have a secondary effect through improvement in irritability.[Canitano and Scandurra 2008] Glutaminergic drugs and oxytocin are currently the most promising but clearly much additional work is required in this area.[Posey et al. 2008]

Pharmacological treatment of comorbid problem behaviours in ASD

Inattention, overactivity and impulsiveness in ASD (symptoms of ADHD): In these associated problems which are signs of ADHD, methylphenidate has been found to be effective in many studies. In general, methylphenidate produces highly variable responses in children with ASD and ADHD symptoms. But it is reasonable to use methylphenidate in children of ASD with symptoms of ADHD with adequate advice to the parents regarding the adverse effects of methylphenidate.

Atomoxetine is also useful in controlling these symptoms in children with ASD, but large scale RCTs are awaited.[Arnold et al. 2006] There is some evidence from controlled studies for risperidone and α₂ agonists (clonidine and guanfacine).

Irritability (aggression, self-injurious behaviour, tantrums): Second generation antipsychotics are the first line pharmacological treatment for children and adolescents with ASD and associated irritability.[Parikh et al. 2008] The only licensed medication is risperidone.[Jesner et al. 2007] The other atypical antipsychotics e.g. clozapine and aripiprazole are under evaluation.

Sleep disturbance: Children with ASD have significant sleep problems.[Krakowiak et al. 2008] Typical sleep problems in this group are sleep onset insomnia, deep maintenance insomnia and irregularities of the sleep wake cycle including early morning awakening. Melatonin has been several small studies to be beneficial in children with ASD with reductions in sleep latency as well as efficiency. Risperidone may benefit sleep difficulties in those with extreme irritability.

Tics and Tourette syndrome

Transient tics as well as Tourette syndrome frequently affect children and adolescents.

Drugs which are tried:

Adrenergic α₂ agonists -- Clonidine and guanfacine have been shown to improve the disability and reduce frequency of tics. However, most of the evidence is derived from open label studies.

Antipsychotics -- Pimozide, haloperidol, risperidone, sulpiride, quetiapine and olanzapine have been tried and are found to be efficacious in treating Tourette syndrome. But side effects of antipsychotics may outweigh beneficial effects in the treatment of tics and so it is recommended that clonidine is tried first.

Other drugs -- Baclofen, nicotine augmentations of haloperidol both were found to be beneficial in overall impairment rather than a specific effect on tics. Pergolide (a D₁-D₂-D₃ agonist), flutamide (an antiandrogen) has been found effective in Tourette syndrome. Case reports or case series describes positive effects for ondansetron, clomiphene, tramadol, topiramate, cyproterone, levatiracetam and cannabis. Tetrabenazine may be useful as add on treatment.

Conduct disorder

Medications are best looked on as adjuncts in the treatment of uncomplicated conduct disorder and may be useful for crisis management and short term intervention. Comorbid conditions and their specific symptoms such as aggression, mood lability, or impulsivity may be targets for psychopharmacological intervention. The best case for medication can be made for the management of comorbid ADHD symptoms with stimulants.

Enuresis

Two medications -- Imipramine and desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated dDAVP) have proven to be efficacious in the treatment of enuresis. Imipramine, in a single bedtime dose 1 to 2.5 mg/kg has been used for many years. dDAVP is a synthetic analogueof the antidiuretic hormone (ADH) vasopressin, which decreases urine production at night when taken at bedtime. It is administered orally in 0.2 mg tablets in doses of 0.2 to 0.6 mg nightly.

Childhood insomnia

Exogenous melatonin is now the first line medication prescribed for childhood insomnia.

Medicines and Health Care Regulatory Agency (MHRA) guidance for risperidone prescribing in children and adolescents

Doses of risperidone in paediatric patients with ASD (by total mg/day)

General considerations

· Risperidone can be administered once daily or twice daily.

· Patients experiencing somnolence may benefit from a switch in dosing from once daily to either once daily dosing at bedtime or twice daily.

· Once sufficient clinical response has been achieved and maintained, consideration may be given to gradually lowering the dose to achieve the optimum balance of safety and efficacy.

· There is insufficient evidence from controlled trials to indicate how long the patient should be treated.

· Adverse effects: Weight gain, somnolence and hyperglycaemia require monitoring and the long term safety of risperidone in children and adolescents with ASD remains to be fully determined.

Doses of commonly used psychotropic drugs in children and adolescents

Liquid fluoxetine: Liquid fluoxetine preparation is used in ASD as treatment can begin with lowest possible dose with monitoring of side effects.

Dose -- Liquid fluoxetine (as hydrochloride) (20mg/5ml) 2.5 mg/day for one week. Follow with flexible titration schedule based on weight, tolerability and side effects up to a maximum dose of 0.8 mg/kg/day.

Adverse effects -- Monitor for suicidal behaviour, self-harm and hostility, particularly at the beginning of treatment. Hyponatraemia should also be kept in mind whenever the child shows drowsiness, confusions or convulsions.

Conclusion

Finally concluding to understand the treatment process in any child and adolescent case, the following treatment planning example is presented:[Sexson 2005]

A 14 years old girl is referred for treatment for a depressive disorder. She has no medical problems or safety issues and was well three months ago.

Biologic: Significant depressive symptoms, including insomnia, poor appetite, fatigue, decreased concentration, sadness, and major irritability with a strong family history of depression.

Psychologic: Patient is very sad and views herself as a failure so she has not been doing her schoolwork. She no longer makes straight As. She feels worse and hopeless when her parents frequently remark about the importance of college to be successful and how all grades in high school count.

Social: Decreased interactions with peers since depressed. History of excelling in extracurricular activities such as yearbook and volunteering. Long term, high functioning close friends call and invite out patient frequently and she refuses to go.

Overall goal: Restore to previous age-appropriate functioning.

Biologic

Immediate

Goal: Consider medication to target medication responsive symptoms. Assess extent and severity of symptoms as well as evaluating the patient’s and family’s view of the disorder and medication.

Intervention: Discuss medication with patient and family as part of a comprehensive treatment; review options in terms of immediate or delayed initiation, advantages and disadvantages of each; the patient prefers to try therapy first and her parents agree.

Monitoring: Obtain information on baseline functioning, symptoms, and Children Depression Inventory (CDI; self report of depressive symptoms); agree that symptoms will be assessed at least weekly, more if necessary.

Outcome: Agree that will try medication if not significantly better after a month of weekly psychotherapy.

Short term

Goal: Start and maintain medication to target symptoms responsive to medication.

Intervention: Review medication options; discuss initiation, possible length, monitoring and criteria for discontinuation of medicine; discuss and agree upon target symptoms; choose a medication, review its advantages and disadvantages, explain appropriate administration; obtain appropriate consent and assent.

Monitoring: Obtain a baseline assessment of targeted symptoms and CDI; agree with patient and family that will monitor symptoms monthly or as needed.

Outcome: Initiate medication, titrate to appropriate dose, monitor response, side effects and ongoing need.

Long term

Goal: Resolution of depressive symptoms, first with medication and eventually without.

Intervention: Ongoing medications along with other treatments.

Monitoring: Monthly assessment of symptoms and functioning along with discussion of need for medication; discussion of possible taper and discontinuation of medication once stable and back to optimal functioning for at least six months.

Outcome: Resolution of depressive symptoms with minimal side effects on medication and restoration of prior functioning; maintenance of functioning and lack of significant depressive symptoms off medication.

Psychologic

Immediate

Goal: Asses the patient’s and the family’s understanding of illness and treatment. Engage patient and family in therapy.

Intervention: Obtain information on patient’s symptoms, level of functioning, and supports as well as data on the dissatisfaction with previous therapy and potential difficulties in participation in therapy. Discuss the general approach to therapy.

Monitoring: Ask for feedback on the initial sessions; discuss any issues or difficulties.

Outcome: Patient and parents agree to weekly psychotherapy.

Short term

Goal: Establish agreement on a problem hierarchy and general psychotherapeutic approaches, and implement and provide ongoing therapy. Establish educational plan with adequate support and realistic expectations for patient.

Intervention: Discuss various problems and agree that patient’s view of herself as failure, her expectations in terms of performance, and their effects on her schoolwork are priorities. Agree that will employ a cognitive-behavioural therapeutic approach with patient (identifying maladaptive thoughts that affect emotions and behaviour and substituting more appropriate thoughts) in individual psychotherapy. Agree that parents will be included on a regular basis to work on relationship issues. Obtain consent and assent and review confidentiality. Contact teacher and obtain information on patient’s functioning and school structure.

Monitoring: Agree that parents will participate in monthly sessions to work on parent-child interactions, at which time the patient’s self-perception will be reviewed as well as her schoolwork issues.

Outcome: Initiate psychotherapy, monitor response, and periodically reassess need for different approach. Explore and decide upon options such as tutoring, modification of classes.

Long term

Goal: Appropriate positive self-view and academic achievement, first with psychotherapy and educational modification and then without.

Intervention: Ongoing psychotherapy along with other treatments.

Monitoring: Monthly assessment of self-image and school achievement along with discussion of need of psychotherapy; discussion of taper and discontinuation of psychotherapy once stable and back to optimal functioning for at least six months.

Outcome: Resolution of feelings of failure and their effect on schoolwork and restoration of prior functioning; maintenance of functioning and lack of significant self-worth and school issues once no longer in psychotherapy.

Social

Immediate

Goal: Establish the resources available to patient for age appropriate activity with peers.

Intervention: Obtain information from patient, parent, and school on prior activities and level of participation as well as currently available opportunities. Also obtain information on patient’s friends and their past and current relationships.

Monitoring: Establish patient’s current baseline of interest in social activities.

Outcome: Patient and parents agree to identify possible and desirable resources.

Short term

Goal: Establish agreement on appropriate activities and friends for patient to increase involvement with.

Intervention: Discuss and develop a hierarchy of activities, beginning with involvement with structured activities (i.e. yearbook) or planned by others (i.e. going out with friends once invited). Review and identify any obstacles (internal or external) and develop intervention strategies. Enlist the involvement of parents, friends, and school to provide opportunities and encourage patient.

Monitoring: Agree that patient’s activities will be reviewed weekly with assessment of progress.

Outcome: Initiate process to help patient resume an appropriate level of social activities with peers, monitor progress, assess need for other interventions.

Long term

Goal: Appropriate social activities first initiated by others and then by self.

Intervention: Ongoing psychotherapy along with interventions by parents, friends, and school.

Monitoring: Monthly assessment of social activities and interactions along with discussion of need for psychotherapy and interventions by others; discussion of possible taper and discontinuation of help by others then psychotherapy once stable and back to optimal functioning for at least six months.

Outcome: Resolution of isolative behaviour and restoration of prior functioning; maintenance of functioning once no longer initiated by others and in psychotherapy.

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