Pharmacological Interventions for Young People

• Focuses on pharmacological interventions, depression management, drug treatments, and antipsychotics in young people within clinical services.

Pharmacological Interventions

• Requires good assessment, formulation, clear indication/rationale, information, monitoring, and use alongside psychoeducation and other interventions.
• Only about 20% of medications are licensed for use in Children and Young People (CYP).
• Off-label medication use is common, though lack of licensing may limit use by clinicians and patients.
• Challenges: limited research, stigma, and consent issues need addressing.
• Practical prescribing involves starting with low doses and increasing slowly.
• CYP are more prone to side effects than adults, particularly those with intellectual disabilities (ID) or neurodevelopmental disorders.
• CYP often need lower medication doses than adults
• Regular monitoring during initiation is essential.
• Combining medications should be avoided.
• Monitoring needs to continue as the child grows, even on maintenance doses

Depression

• Lifetime prevalence by the end of adolescence is 20%
• Recurrence is common with impacts on future mental health
• Requires appropriate and comprehensive treatment
• For moderate-severe depression, NICE guidelines recommend referral to CAMHS and psychological interventions like CBT, IPT, family therapy, or psychodynamic psychotherapy.
• Psychological interventions should be discussed with the young person and their family.
• If there is no response after 4-6 sessions, consider alternative therapies or adding medication
• Antidepressant use should be reviewed by an expert and combined with psychological interventions.
• Fluoxetine is recommended as the first-choice medication.
• Ensure frequent follow-ups (weekly for the first 4 weeks).
• Patients should be informed about rationale, delay in effect onset, treatment duration, adverse effects, and prescribed medication adherence.
• Written information should be provided.

Drug Treatments for Depression in CYP

• If there is a response to the medication, continue prescribing for 6 months after remission.
• Remission is defined as no symptoms and full functioning for at least 8 weeks.
• If there is no response to Fluoxetine, consider Sertraline or Citalopram
• Antidepressants can be used for anxiety, OCD, and chronic pain
• Most studies of antidepressants focus on adolescents.
• Treatment should combine psychological intervention with medication.
• Antidepressants should be prescribed and monitored by a child and adolescent psychiatrist.
• NICE recommends SSRIs antidepressants.
• SSRIs are the most common antidepressants
  • Examples include Fluoxetine (Prozac), Sertraline, Citalopram/Escitalopram, and Paroxetine.
• In the UK, only Fluoxetine is licensed for depression in those older than 8 years, Sertraline, Citalopram
• Fluoxetine, Sertraline, and Citalopram are the only SSRIs with consistent efficacy in young people.
• Common side effects of SSRIs are transient and may occur before perceived effect
• Common side effects include GI upset, headaches, anxiety, tiredness, insomnia, and erectile dysfunction.
• Rare side effects include increased risk of self-harm.
• SSRIs can cause mania in those at risk or with bipolar affective disorder (BPAD)
• Additional side effects: seizures, galactorrhea, clotting abnormalities and anaphylaxis
• Serotonin syndrome signs include changes in blood pressure (BP), fast/irregular heart rate (HR), high temperature, sweating/shivering, confusion, restlessness, muscle twitching, tremor, nausea, and vomiting; seek medical advice urgently.
• Take SSRIs with food.
• Be aware of mixing SSRIs with other medications, like OTC drugs, and warn about pregnancy
• Use caution combining SSRIs with alcohol or recreational drugs
• Do not take more than the prescribed dose
• Specialist prescribing is recommended for other antidepressants like Mirtazapine, Venlafaxine and Duloxetine, as there is a lack of evidence of their efficacy
• Tricyclic antidepressants are older and less commonly used in adults
  • Examples include Amitriptyline and Nortriptyline
  • They have many side effects and are toxic in overdose Clomipramine is a tricyclic used for OCD with good evidence.

Practical Prescribing

• Start and increase doses slowly
• Stop and monitor for discontinuation symptoms
• Use liquid preparations if needed
• Monitor treatment effects, some people benefit within 1-2 weeks, most see effects in 2-6 weeks, review if no effect at 4 weeks
• Gradually wean to stop medication, wait seven days, then start another one
• Review the plan if the antidepressant isn't working, reconsider formulation, psychological intervention, and social factors
• Ways to administer medication:
  • Increase the dose, but note the risk of side effects
  • Switch SSRIs, NICE recommends sertraline or citalopram (Brent et al., 2008)
    • Adult studies suggest this may be less successful
    • Use augmentation, but this is only done by specialists - adding another medication to the treatment
• NICE guidelines
• Zhou et al., 2015 indicates its use, especially in psychosis or Bipolar depression
• Lithium is used, but there are no adolescent studies

Antipsychotics and Psychosis

• Antipsychotics are used for psychosis, schizophrenia, mania, and BPAD
• They can be used for rapid tranquilization under separate protocols.
• Lower doses may be suitable for aggression in autism, conduct disorder, intellectual disability, Tourette's, and OCD.
• Atypical antipsychotics (SGAs) and typicals (FGAs) are used for treating this
• Treating with medication is a component of care, as it reduces long-term challenges and aids recovery.
• Functional improvement is key to long-term outcomes.
• Other interventions: psychoeducation, individual therapy (CBT), occupational and functional improvement
• Family work, diet, and lifestyle interventions are good to implement
• These medications treat psychosis in Children and Young People (CYP), but the effects are modest with treatment resistance being common.
• Confirmed by NMAs, atypicals are prescribed more often.
• There is little evidence showing they're better than typicals, the side effects differ and lower doses can be better

Side Effect Profiles

• Yao (2003) found that risperidone had less extrapyramidal symptoms (EPS) than haloperidol
• Sikich (2004) the BPRS-C improved in risperidone 74%, olanzapine 88% & haloperidol 54%. Weight gain was significant in all patients
• Sikich (2008) found no differences - more weight the CYP gained with olanzapine
• Haas (2009) found that risperidone was better than placebo, But more side effects at higher doses
• General side effect: sedation, lower blood pressure, movement issues, metabolic issues, increased prolactin, and QTc
• Conduct disorder medication should not be used, unless treating comorbidities such as ADHD
  • Risperidone should be considered
  • Clear expectations of the benefits are needed
  • Discontinue it if there's no clinical response following 6 weeks
  • Behaviours can be aggressive, angry and emotionally unregulated

Eating Disorders

• There is no real evidence of medication benefits to Anorexia Nervosa
• Comorbidities like depression, do need addressing

Paediatric Bipolar Affective Disorder

• Conditions: mania and hypomania
• Medications: atypical antipsychotics such as aripiprazole, risperidone, olanzapine, and quetiapine.
• Baseline bloods, ECG, and pregnancy tests required when using lithium due to teratogenic effects
• Combining antipsychotics and lithium is a common therapy
• Valproate, carbamazepine, and lamotrigine can be added as anti-epileptic medications
• Antipsychotic and if severe with an SSRI can treat depression
• It is best to use Olanzapine and Fluoxetine, according to evidence, for at least 1-2 years
  • Antipsychotics (First-Line), Lithium (Second-Line), and anti-epileptics maintain effects
• ECT can be used if someone is having a severe, persistent, and disabling bipolar state, as well as a poor medication response
• SSRIs are the only recommended pharmacological intervention for depression in Children and Young People, as recommended by NICE
• Only Fluoxetine is licensed but others can be used
• SSRIs are prescribed and monitored by a child and adolescent psychiatrist
• Mixed Evidence
• Evidence 1
  • Bridge demonstrated the meta-analysis and RCTs of a paediatric antidepressant treatment
    • Effectiveness was 61% vs 50; NNT was 10 (95% CI 7-15)
  • Hetrick 2007 – Cochrane review and meta-analysis Relative risk of remission: 1.31 (95%CI 1.17 – 1.41)
  • Hetrick reported effect sizes from a 2021 Cochrane review
• This showed significant heterogeneity between SSRIs, different pharmacological actions and different trial methodologies
• Evidence 2:
  • Clinical significance
    • The range of Fluoxetine vs placebo difference was 5.34 on CDRS (range 17-113), based on meta-analysis
    • Using the TADS to treat Adolescents with Depression
      • (N = 221), the difference in response rate was found to be 26%
      • NNT was 4, and the antidepressant and psychological benefits worked well together
• trials usually exclude severe depression/suicidality like Davey (2019) and Goodyer (2007/2017).
• Kirsch states the placebo effect, and that that placebo response is lower in more severe depression
• Zhou et al 2020 said Fluoxetine alone, or with CBT has best evidence in cases 71 trials, 9510 participants shows limited evidence for other SSRIs, despite the similar sample sizes (HOWEVER across all studies), with limited evidence in those with severe depression

Discontinuation Effects

• Warn patients about discontinuation and it's effects Discontinuation = days vs weeks
• Side effects can include electric shocks, tingling, dizziness, GI upset, headache, anxiety and flu-like symptoms
• Sharma reported significant increase rates (OR 2.39), but its not clear that medication causes it
• General findings shows: suicides decreased when SSRI used increased Findings by
  • Gibbons (2007)
  • Wheeler (2008)
  • Simon (2008)
  • Li (2022)
  • Lagerberg (2022)
• Conclusions: small in CYP risk compared to placebo treatment needs a risk balance, with evidence is either varying, and inconsistent
• Warn those who have activating or risks from CYP; antidepressants can treat depression to the appropriate
• Other details include psychological intervention, and honest communication and that these common side effect may not last A presentation of:
  • increased social isolation, low more and anxiety and unclear history can show low moods, self-neglect, etc. Medication:
  • Assess with temperament, genetics and/or family history and previous experiences
  • Consider problems with verbal communication
• Consider intellectual disability, verbal comprehension

Antipsychotics

• Prefer atypical over typical cases, as well as presenting individual choices
• Must ideal be discussed with family, and in family environment
• Common Medication side effects: movement disorders, gaining weight, elevated prolactin levels, heart problems
• Should monitor weight
• If weight is being gained, measure and consider lifestyle changes such as avoiding small options, keeping an eye on fiber, and incorporating exercise (+ family)

NICE GUIDELINES

• Most recommend treatment for 1-2 with/after full recovery without relapse, gradual withdrawal and monitoring for 2 years after cessation
• Side effects: weight gain, nausea, constipation, heart issues and fever.
• Neutrophils/Agranulocytosis - low counts with symptom infections, as well as fatality risks for +1 treated patient
• Be consistent and check-in to monitor: can use similar medication rates and have them contrast
• Use only if there is a risk of complications: delays of up to 47 months with dosages
• Can have 40% of patients due to age that are unfamiliar Offer Clozapine to children and young people whose illness has not responses adequately to pharmacological treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs each used for 6-8 weeks
• Usually starts with Risperidone, Olanzapine or Aripiprazole