Use of selective serotonin reuptake inhibitor medications for the treatment of child and adolescent mental illness

Question 1

What medications are included in the SSRI class?

Answer 1

1. Fluoxetine
2. Sertraline
3. Citalopram
4. Escitalopram
5. Fluvoxamine
6. Paroxetine

Question 2

What is the mechanism of action for SSRI?

Answer 2

Inhibit serotonin transporters, blocking reuptake and increasing concentration of the neurotransmitter serotonin within the synapse

Question 3

Is absorption of SSRI affected by ingestion of food?

Answer 3

No

Question 4

How is SSRI absorbed and metabolized?

Answer 4

Through the liver

Question 5

Are laboratory investigations routinely indicated before initiating or maintaining SSRI medication use?

Answer 5

No

Question 6

What are indications for laboratory investigations?

Answer 6

1. To r/o alternative underlying etiologies of the presenting symptoms e.g. hypothyroidism
2. Assess comorbid medical conditions e.g. hepatic impairment
3. Monitor therapeutic drug levels of medications used in combination with SSRI medication e.g. valproic acid

Question 7

Which SSRI has the highest and which has the lowest reports of discontinuation/withdrawal symptoms?

Answer 7

Paroxetine highest

Fluoxetine fewest

Question 8

What are the half lives for SSRI?

Answer 8

1. Fluoxetine 96h
2. Sertraline 26h
3. Fluvoxamine 15h
4. Citalopram 35h
5. Escitalopram 30h
6. Paroxetine 21h

Question 9

What is the response rate for SSRI in the treatment of adolescent depression?

Answer 9

40-70%

Question 10

Among children <12yo which SSRI have demonstrated benefits over placebo in treating pediatric depression?

Answer 10

Only fluoxetine

Question 11

Among adolescents, which SSRI have demonstrated benefits over placebo in treating pediatric depression?

Answer 11

Escitalopram
Fluoxetine
Some efficacy for citalopram and sertraline

Question 12

In the Treatment for Adolescents with Depression Study (TADS) comparing placebo, CBT alone, fluoxetine alone, and combination fluoxetine + CBT which arms weere most effective?

Answer 12

Fluoxetine alone was more effective than CBT alone or placebo

Fluoxetine alone and Fluoxetine and CBT were equally efficacious

Question 13

What are some short term side effects of SSRI?

Answer 13

Side effects are dose dependent and decrease over time:
1. GI symptoms
2. Sleep changes e.g. insomnia or somnolence, sleep disturbances, vivid dreams
3. Restlessness
4. Headaches
5. Appetite change
6. Sexual dysfunction
Rare but important side effects:
1. Increase agitation or impulsivity
2. Hypomania in children risk of bipolar disorder
3. Increased risk of bleeding
4. SIADH
5. Serotonin syndrome/Toxicity
With citalopram >40mg/day:
1. QT interval prolongation
2. Risk of arrhythmia

Question 14

What are the symptoms of serotonin syndrome?

Answer 14

1. Mental status changes
2. Myoclonus
3. Ataxia
4. Diaphoresis
5. Fever
6. Autonomic dysregulation

Question 15

What populations should not be prescribed citalopram?

Answer 15

1. Absolute: Congenital long QT syndrome
2. With caution: Underlying congenital heart disease or hepatic impairment (affecting citalopram metabolism) incld. predisposition to cardiac arrhythmia due to electrolyte disturbances as risk of torsades de pointes

Question 16

What does the research state regarding the association of SSRI with suicidality?

Answer 16

1. The potential benefits of SSRI use outweigh the potential harms for the treatment of depression in children and adolescents.
2. Untreated depression is more likely to result in harm than appropriate SSRI use.
3. Close initial monitoring, along with careful documentation of symptoms and adverse effects, are required.

Question 17

What are the FDA suggestions regarding clinical monitoring of patients occur at least?

Answer 17

1. weekly for the first four weeks following initiation of SSRI medication;
2. every two weeks for the next four weeks;
3. at 12 weeks;
4. then as clinically indicated beyond the 12-week point.[

Question 18

How long should an SSRI be continues once complete response is achieved and why?

Answer 18

Minimum 6-12m

To reduce risk of relapse

Question 19

How should SSRI be discontinued?

Answer 19

Slow taper to prevent relapse or withdrawal symptoms

Question 20

Which children may warrant a psychiatric consultation before medication discontinuation?

Answer 20

1. History of multiple depressive episodes
2. Comorbid psychiatric illnesses
3. Complex depressive e.g. with psychotic features

Question 21

What are the key messages regarding SSRI in the treatment of child and adolescent depressive disorders?

Answer 21

1. Of the SSRI medications, fluoxetine has the most data supporting its use for treating depression in children and adolescents.
2. Citalopram should not be used in dosages >40 mg/day.
3. Citalopram should be prescribed with caution in certain individuals (described above), and should not be prescribed for children and adolescents with congenital long QT syndrome.
4. The risk of suicidality associated with untreated depression is likely greater than that associated with appropriate SSRI use.

Question 22

Which medications have proven effectiveness in the treatment of generalized anxiety disorder in children and adolescents?

Answer 22

1. Fluoxetine (7-17yo)
2. Sertraline (5-17yo)
3. Fluvoxamine (6-17yo)

Question 23

Which medications have proven effectiveness in the treatment of selective mutism in children and adolescents?

Answer 23

Fluoxetine (6-11yo)

Question 24

Which medications have proven effectiveness in the treatment of social phobia in children and adolescents?

Answer 24

1. Fluvoxamine (6-17yo)

2. Paroxetine (8-17yo)

Question 25

Which medications have proven effectiveness in the treatment of separation anxiety disorder in children and adolescents?

Answer 25

Fluvoxamine (6-17yo)

Question 26

What are the key messages regarding the use of SSRI in the treatment of anxiety?

Answer 26

1. SSRIs may be considered early in the course of treatment for anxiety disorders if anxiety is severe or causing significant functional impairment, or if the child is unable to benefit from psychotherapy.
2. Careful elicitation and documentation of physical symptoms of anxiety should be completed before initiating medication.
3. To improve tolerability of medication for anxious patients, clinicians should include the following in their overall approach:
   a) Psychoeducation
   b) Lower starting dosages
   c) Gradual titration to therapeutic dosages.

Question 27

What are the summary and recommendations regarding the use of SSRI in pediatrics?

Answer 27

1. When undertaken following an appropriate clinical assessment, and within the context of a comprehensive management plan, SSRI medications may be effective in the treatment of child and adolescent depression and anxiety disorders.
2. Because depression in particular is associated with high rates of suicidal ideation, behaviour and completed suicide, untreated illness may be more harmful than appropriate use of SSRI medication.
3. Before initiating pharmacotherapy, physicians should carefully elicit and document baseline depressive and anxious symptoms.
4. Following medication initiation, patients should be closely monitored for potential adverse effects, including suicidal ideation and behaviour.