This medication treatment algorithm outlines evidence-based pharmacological interventions for adolescent depression, incorporating safety considerations, efficacy, and potential adverse effects. The algorithm can serve as a guide and should be individualized based on clinical judgment, patient preferences, and specific clinical circumstances. Regular monitoring and reassessment are essential throughout the treatment process.

Step 1: Initial Assessment

• Comprehensive Evaluation: Conduct a thorough assessment, including psychiatric history, symptom severity, medical history, family history, and suicidality risk. Consider differential diagnosis and co-morbidities.
• Psychotherapy: Initiate or continue evidence-based psychotherapy, such as cognitive-behavioral therapy (CBT) or interpersonal therapy (IPT). Inform psychotherapist of planned psychopharmacologic treatment and maintain ongoing collaborative dialogue as warranted
• Education and Informed Consent: Educate the patient and their family about the potential benefits, risks, and side effects of medication treatment. Obtain informed consent.

Step 2: First-Line Pharmacotherapy

• Selective Serotonin Reuptake Inhibitors (SSRIs):
  • Fluoxetine: Start with a low dose (10 mg/day) and titrate gradually to therapeutic range (20-60 mg/day).
  • Escitalopram: Initiate at 5-10 mg/day, titrate up to 10-20 mg/day.
  • Sertraline: Begin with 25-50 mg/day, titrate up to 50-200 mg/day.
• Monitoring:
  • Close monitoring for therapeutic response and adverse effects, especially during the first 4-6 weeks and following future dose increases, if instituted.
  • Assess for emergence or worsening of suicidal ideation, agitation, or behavioral activation.

Step 3: Treatment Response Assessment

• Response Evaluation: Evaluate response to SSRI treatment after 4-6 weeks.
• Adjustment: If partial response or inadequate response, consider:
  • Increasing SSRI dose, gradually at q 2-4 week intervals.
  • Switching to another SSRI.
  • Adding psychotherapy or non-pharmacological interventions.

Step 4: Second-Line Pharmacotherapy

• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):
  • Venlafaxine: Initiate at 37.5 mg/day, titrate up to 75-225 mg/day.
  • Duloxetine: Start with 30 mg/day, titrate up to 60-120 mg/day.
  • Bupropion: Consider in cases with atypical depression symptoms or when SSRIs or SNRIs are ineffective or not tolerated. Begin with 75 mg/day, titrate up to 150-300 mg/day.
• Monitoring:
  • Continuously monitor for therapeutic response and adverse effects.
  • Assess for potential drug interactions, especially with other psychotropic medications.

Step 5: Consultation and Collaboration

• Collaboration: Maintain open communication with the patient, their family, and involved healthcare professionals throughout treatment.
• Consultation: Consider consultation with a child and adolescent psychiatrist for complex cases, treatment-resistant depression, or significant comorbidities.

Step 6: Continuation and Maintenance

• Continuation Phase: Once remission is achieved, continue the effective medication at the same dose for at least 6-12 months to prevent relapse.
• Maintenance Phase: For recurrent depression or chronic conditions, consider long-term maintenance treatment with medication and/or psychotherapy.

Safety Considerations:

• Suicidality Risk: Monitor closely for emergence or worsening of suicidal ideation, especially during the initial weeks of treatment.
• Serotonin Syndrome: Educate about symptoms and signs, especially if combining SSRIs or SNRIs with other serotonergic medications.
• Drug Interactions: Be cautious with concomitant use of other medications metabolized by cytochrome P450 enzymes. Avoid monoamine oxidase inhibitors (MAOIs).
• Monitoring Parameters: Regularly assess for efficacy, adverse effects, vital signs, and growth parameters in adolescents.

Author:

Shawn Singh Sidhu, M.D., DFAPA, DFAACAP

​Medical Co-Director, Vista Hill Foundation

References:

• American Academy of Child and Adolescent Psychiatry (AACAP). (2019). Practice parameter for the assessment and treatment of children and adolescents with depressive disorders.
• Cheung, A. H., & Emslie, G. J. (2015). Treatment-resistant depression in adolescents. Pediatric Drugs, 17(6), 383-392.
• National Institute for Health and Care Excellence (NICE). (2019). Depression in children and young people: identification and management (Clinical guideline [CG) 28).
• Zhou, X., Hetrick, S. E., Cuijpers, P., Qin, B., Barth, J., Whittington, C. J., … & Xie, P. (2015). Comparative efficacy and acceptability of psychotherapies for depression in children and adolescents: A systematic review and network meta-analysis. World Psychiatry, 14(2), 207-222.
• Baldwin, D. S., & Montgomery, S. A. (2005). Serotonin selective reuptake inhibitors. Journal of Psychopharmacology, 19(2_suppl), 4-6.
• Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., … & Fava, M. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American Journal of Psychiatry, 163(11), 1905-1917.
• Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., … & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet, 391(10128), 1357-1366.
• Taylor, D., Paton, C., & Kapur, S. (2019). The Maudsley prescribing guidelines in psychiatry. John Wiley & Sons.
• Nutt, D. J. (2008). Relationship of neurotransmitters to the symptoms of major depressive disorder. The Journal of Clinical Psychiatry, 69, 4-7.

 First, it is important to determine what makes anxiety clinically significant. Anxiety is an expected, normal, transient response to stress and can be helpful with the warning of danger or coping with the stress. Clinically significant anxiety is an excessive response to external stress or related to an unidentifiable trigger. It is persistent rather than transient. It causes functional impairment, by exceeding the patient’s ability to cope with the stress and/or leading to avoidance behaviors.

 General symptoms of anxiety in children include many worries about things before they happen, constant worries or concerns about family, school, friends or activities, fears or embarrassment or making mistakes, low self-esteem and lack of self-confidence. There are often somatic complaints as well, like stomachaches, headaches, and sleep disturbance, as well as a desire to avoid school and friends.

 Specific symptoms of separation anxiety include constant thoughts and intense fears about the safety of parents and caregivers, refusing to go to school, frequent stomachaches and other physical complaints, extreme worries about sleeping away from home, being overly clingy, panic or tantrums at times of separation from parents, trouble sleeping or nightmares, and refusing to sleep without parents.

 Specific symptoms of a phobia include extreme fear about a specific thing or situation (ex. dogs, insects, needles) and the fears cause significant distress and interfere with usual activities (ex. child refuses to go to the park because of a fear of seeing a dog).

 Specific symptoms of social anxiety include fears of meeting or talking to people, avoidance of social situations despite a desire to attend, and few friends outside the family.

 Anxiety disorders have a high rate of co-morbidity with other psychiatric disorders, primarily mood disorders, ADHD and other disruptive behavior disorders, and substance use disorders. It is therefore important to assess for these co-morbidities. To complicate things further, there can be some overlap with the specific symptoms of anxiety and other psychiatric disorders. For example, patients with Generalized Anxiety Disorder may “obsess” about daily worries, patients with Autism Spectrum Disorders have rituals, and patients with Major Depressive Disorder may ruminate or “obsess” over negative self-thoughts, but it does not mean that these patients also have Obsessive-Compulsive Disorder.

Treatment options primarily involve therapy and/or medication. For patients presenting with mild-moderate anxiety symptoms, a therapy approach first is preferred, with a plan to incorporate medication if the therapy is not effective or symptoms worsen. For patients with moderate-severe anxiety symptoms with significant impairment on daily functioning, it might be warranted to consider starting with a combination of medication and therapy. The key message is that therapy is the important component to treatment of anxiety disorders in pediatric patients, and medication can be an effective adjunctive treatment if needed. Therapy to address anxiety can easily be tailored to work with very young patients and is very effective in a dyadic format . Types of therapy used for anxiety disorders include: cognitive behavioral therapy, exposure response prevention therapy, and relaxation techniques, among others. It would be important to refer to a therapist who is well versed in treating anxiety in children and adolescents.

Now we will focus on the medications used to treat anxiety. They fall into two general categories: medications to treat the underlying anxiety and prevent future symptoms of anxiety and medications that treat acute symptoms, like a panic attack. In most cases, if a primary care provider is considering medication treatment for anxiety in a young patient, it will be from the first category. This category includes medications like the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazipine, and buspirone. The SSRIs are the first line agents for this population. This class includes: fluoxetine, citalopram, escitalopram, sertraline, fluvoxamine, and paroxetine. Just like with treating depression, the medication can take 4-6 weeks to see the positive effective. Often a higher dose is needed to fully treat the anxiety symptoms compared to depressive symptoms. There is a motto to “start low and go slow” to limit increasing anxiety and causing activation during the titration process. So, for example if one is considering prescribing citalopram for anxiety for a 10 year-old patient, consider starting at 5 mg qday for one week then 10 mg qday for 1 week then 20 mg qday and assessing the response. Some patients experience akathisia (internal feeling of restlessness), which can feel like a worsening of their anxiety, if the dose is titrated too quickly. Other side effects include sleep disturbance, GI upset and headache but most of these symptoms resolve over time.

The treatment of anxiety disorders in pediatric patients is mostly off label. Only fluoxetine (ages 7+), sertraline (ages 6+) and fluvoxamine (ages 8+) have FDA approval for treatment of obsessive-compulsive disorder (OCD).

When prescribing any antidepressant medication to treat anxiety, it is important to review the FDA black box warning about the increased risk of spontaneous reporting of suicidal thoughts, even if the medication is not being prescribed to treat depression per se.

When deciding on medication treatment, it is standard practice to first use the SSRIs. If a patient has 2 or more adequate (in terms of dose and length of treatment) trials of SSRIs that are ineffective, one could consider an alternative, either an SNRI (venlafaxine or duloxetine) or mirtazipine. If there is some benefit from the SSRI, one could consider augmentation with mirtazipine or buspirone. The primary side effects to be concerned with mirtazipine include sedation and increased appetite. Buspirone has an onset of action of about 2 weeks. The primary side effects to be concerned with include: dizziness, fatigue and GI upset. Occasionally the atypical antipsychotics are considered as adjunctive treatment to treatment-resistant OCD.

The medications that treat acute symptoms of anxiety, like the benzodiazepines, are rarely used in this population. Pediatric patients can have a paradoxical reaction to benzodiazepines and exhibit behavioral disinhibition. Other side effects include: physiological and psychological addiction, confusion, sedation and impaired fine motor coordination. If a medication to treat acute anxiety is needed, for example for a teenager who has very occasional panic attacks, one could consider hydroxyzine 25-50 mg on a prn basis (available in 10mg tablets as well for younger patients), which is not associated with dependence. Side effects include: sleepiness, dizziness, and dry mouth.

It is important for primary care providers to be comfortable assessing anxiety symptoms and helping to establish a treatment plan for their pediatric patients. Sometimes rating scales can be helpful in the assessment process. Here is a useful screening tool with a child version and parent version:

http://www.midss.org/sites/default/files/scaredchild1.pdf

http://www.midss.org/sites/default/files/scaredparent1.pdf

Hopefully this series of articles has been a helpful tool to establish a level of comfort to assess and treat anxiety syndromes in the primary care setting.

It is important to thoroughly assess for other causes for the hallucinations before considering a psychotic disorder because primary psychotic disorders are very rare in children. It is important to conduct a thorough clinical history and physical exam, and to consider basic labs and/or brain imaging if there are other signs of a medical or neurological process. Medical causes for hallucinations include: seizures, brain tumors (particularly in the visual association areas, temporal lobes and area around the optic nerve and retina), thyroid disease, electrolyte imbalances and adrenal disorders.

Medications that can commonly cause hallucinations include steroids, anticholinergics, and stimulants. It is important to consider the possibility of illegal drug use, including marijuana, even in very young children, who may have either taken the drug on purpose or ingested it accidentally. Visual, olfactory and gustatory hallucinations in children may suggest a medication or substance-related cause. It is important to rule out hypnagogic hallucinations, which occur immediately before falling asleep and hypnopompic hallucinations, which occur during the transition from sleep to wakefulness, both of which are normal phenomena.

True hallucinations in children are more likely to be a part of a non-psychotic psychiatric disorder than a primary psychotic disorder. Hallucinations can occur in children with non-psychotic psychiatric disorders, like depression, anxiety, and disruptive disorders. Hallucinations are not uncommon in depression in children but may suggest a higher risk for developing bipolar disorder. It is common for grieving children to hear “voices” from recently deceased loved ones. It’s important to remember that children who have experienced trauma can experience hallucinations as part of the trauma reaction. Hallucinations are common in children with developmental delays, including autism spectrum disorder. Children with language disorders may talk about “voices” because they cannot describe their own thoughts. In these situations, it can be helpful to ask a child if s/he is experiencing the voice inside of outside his/her head.

After ruling out the above, one can consider a primary psychotic disorder. It is important to assess for other psychotic symptoms (like disorganized speech, bizarre behavior, delusions, paranoia) as well as negative symptoms of psychosis (apathy, amotivation, and decline in functioning) before assuming a primary psychotic disorder, because a diagnosis of a primary psychotic disorder should not be made based on hallucinations alone.

In conclusion, while the report of hallucinations in children is worrisome, it is unlikely that it represents a psychotic disorder. It is important to conduct a thorough history to determine the underlying cause of the reported symptom.

Decreased appetite:
If your patient’s appetite decreases after taking ADHD medicine, advise the parent to give the morning dose after breakfast so that the youth will eat better in the morning. Also advise them to serve a large dinner in the evening when the medication is beginning to wear off. Have them keep healthy, high-calorie, protein snacks on hand for whenever a child asks for food, even if it is before bedtime. Discuss with parents that it is more important to monitor the child’s weight than his day-to-day appetite. Advise them to let you know if the child’s poor appetite lasts for a long period, and consider reducing the dose or stopping the drug on weekends or summer breaks to allow appetite and food intake to return to normal.

Stomach pain or upset:
Advise parents not to give the medication on an empty stomach. Taking the medication with or immediately after food can be helpful for this side effect.

Sleep problems:
Parents should set up a regular bedtime routine that includes calming activities, such as bathing or reading.  Makes sure that a long-acting stimulant is only given in the mornings, typically no later than 10am, and an afternoon dose of a short-acting stimulant should typically not be given later than 3pm. If the sleep disturbance persists, the provider could consider switching from a long-acting to a shorter-acting form or reducing the dose or stopping an afternoon dose.

Daytime drowsiness:
If a child is taking atomoxetine (Strattera) or guanfacine (Tenex/Intuniv) or clonidine (Catapres/Kapvay) and experiences daytime sleepiness, consider giving the medication at bedtime instead of in the morning.  The provider could also consider lowering the dose or dividing the dose and giving it twice a day. 

Rebounding effects:
When an ADHD medication wears off in the afternoon or evening, some children have a period of more ADHD symptoms or irritability and moodiness.  This is more common with the stimulant medications than the non-stimulant medications. To prevent this “rebounding” consider using a longer-lasting medication or prescribing a small dose of fast-acting stimulant later in the day.

Mood Changes:
Make sure the parents are keeping an eye out for changes in the child’s mood and anxiety.  Stimulant medications can negatively affect mood symptoms and anxiety. If that does occur, consider using a non-stimulant medication instead to address the ADHD symptoms.

Finally, it is often advisable to schedule medication initiation or dosage changes to occur on weekends when parents can better monitor for side effect emergence

It is our hope that this practical primer on addressing the common side effects for ADHD medications is helpful to address problems that may arise in the primary care office. And remember providers can contact is at SmartCare for real-time consultation on particular cases.

7 year old boy with chief complaint of “frequent meltdowns”. Additional history: daily meltdowns (crying, hitting) with loud sounds or when asked to wear certain clothing; wants to make friends but poor boundaries and accidentally hurts peers at school when he is playing with them; hard time sitting during seat work at school and prefers to move around when doing his work. There is no known language delay or cognitive delay.

It is thought that the prevalence of Sensory Processing Disorder (SPD) is from 5-15% of school-aged children. SPD is commonly misunderstood and either under-diagnosed or misdiagnosed as Autism or Attention Deficit Hyperactivity Disorder (ADHD). While children with Autism commonly have sensory processing difficulties, it is different than for children with SPD.

Sensory processing is how the nervous system manages incoming sensory information and generates responses. Sensory integration is how the body’s eight senses work together to create the body’s responses. The eight senses include:

A child is diagnosed with a SPD when there is difficulty taking in and interpreting sensory information so that an appropriate response can be generated. Here are some indicators that there might be a concern for SPD.

1. Hyper-acute hearing
2. Hypersensitive hearing
3. Touch aversion
4. Poor motor coordination
5. Poor sense of boundaries
6. High pain tolerance
7. Aggression
8. Distractibility
9. Delayed language development
10. Difficulty learning new things

It is not hard to see how these children can be misdiagnosed with Autism or ADHD. Children with Autism also have impairments in communication, social interactions and present with repetitive behaviors and restricted interests, symptoms that are not seen in SPD alone. Children with ADHD present with hyperactivity, impulsivity and inattention without other sensory processing difficulties.

The behavioral symptoms that are seen with SPD (namely aggression, distractibility, difficulty learning new things) occur as a result of the sensory processing difficulties. Sensory input is organized in a manner that enables an individual to establish a sense of where the body is in time and space, to feel safe in one’s own body and to accurately perceive the body’s relationship to the environment. When this doesn’t happen, it can lead to poor arousal regulation. One significant problem is that SPD is not identified as a diagnosis in the DSM, making it difficult to diagnose. Another barrier is that psychiatrists and medical professionals in general are not well trained in diagnosing SPD.

The goal of this e-Weekly article is not to make all of us experts in SPD and other sensory challenges, but to help us to be better aware when the concern might be there and refer for an appropriate evaluation, most likely with an occupational therapist, who are trained to diagnosis SPD and other sensory challenges and make recommendations for the appropriate treatment.      

Depression is highly co-morbid with other psychiatric disorders, like anxiety disorders, substance abuse disorders and disruptive behavior disorders. If an adolescent is presenting with depressive symptoms, it is important to take a careful history of bipolar symptoms, including current and past manic, hypomanic or psychotic symptoms, family history of bipolar disorders, and history of medication-induced manic or hypomanic symptoms. Twenty percent of young patients with depression go on to develop bipolar disorder as adults. The typical timeline is that adults with bipolar disorder will report they first experienced depressive symptoms starting in childhood or adolescence.

Adolescents will sometimes turn to drugs, like alcohol and marijuana, to self-medicate. If they are using on a regular basis, the use can be contributing to their depressive symptoms, and psychoeducation about that interaction will be important. Ongoing regular drug use can also limit the efficacy of a medication treatment for depression, if that is being considered, and it is important to talk with teens about limiting their drug use if they are interested in a medication intervention.

In terms of general treatment guidelines, consider therapy alone for mild-moderate symptoms and consider combination therapy and medication treatment for moderate-severe symptoms, particularly if there is a significant impairment from their symptoms. Fluoxetine is the medication that has been studied the most for MDD in children and adolescents but the other SSRIs, like citalopram, escitalopram and sertraline, can also be utilized. Other options to consider are bupropion and mirtazapine. The antidepressants to consider avoiding include: paroxetine and venlafaxine (because of their short half-lives, there is a higher risk of side effects and discontinuation symptoms with inconsistent use), and duloxetine (because of limited data in children and adolescents). It is important to consider a slower titration, starting with ½ the usual starting dose, to minimize the risk of side effects including akathisia (internal restlessness), behavioral activation and increased anxiety. So for example if considering fluoxetine, a starting dose of 10mg qday would be appropriate with a plan to increase to 20mg after 1-2 weeks if tolerated and needed. It is important to discuss the length of time it can take for a patient to see a full positive result, so that the teen and family is realistic with their expectations. It is also important to carefully discuss with the teen and family the FDA black box warning about the increase in risk of spontaneous reporting of suicidal thinking and have close monitoring (follow-up in 1-2 weeks either in person or by phone), particularly when medication is started or when the dose is being increased.  With open disclosure and judicious monitoring this relatively infrequent side effect can comfortably managed, typically without having to terminate the medication trial.

It is our hope that this e-Weekly is helpful for primary care providers to develop comfort with assessing and treating adolescents with depression, as it is a fairly common presenting concern in the primary care office.

One such program named Preventure, based at the University of Montreal, looks at these 4 primary traits:

1. Sensation-seeking
2. Impulsiveness
3. Anxiety sensitivity
4. Hopelessness

Three of these are linked directly to mental health concerns. Impulsivity is commonly seen in people with Attention Deficit Hyperactivity Disorder (ADHD). Anxiety sensitivity refers to being overly aware and frightened of physical signs of anxiety, and is commonly seen in panic disorder and to a lesser extent other anxiety disorders. Hopelessness is a symptom of depression. One way to look at this is that most at-risk children can be spotted early, if they present with these symptoms, with early interventions to improve these risky traits.

It is also important to keep in mind that a teen who turns to drugs because of hopelessness has different expectations than a teen to turns to drugs for thrills. Distorted cognitive thinking plays a role for some adolescents who turn to drugs.

In the Preventure model, teachers are educated about these traits and students are taught ways to manage their problematic traits in a general educational workshop approach without being called out for being “at risk”. One hypothesis is that the teacher training helps make teachers more empathic to high-risk students thereby increasing their connection to their school community, which has been shown to decrease drug use.

Studies that have looked at this model have shown a decrease in binge drinking, frequent drug use, and alcohol-related problems. Other studies have shown improvement in non-addiction symptoms as well, including depression, panic attacks and impulsive behavior, which are direct sequelae of the identified 4 high-risk traits.

The idea that identifying and addressing high-risk traits for addiction can be impactful for children and adolescents is a hopeful one and can be implemented across settings, including schools, communities and medical homes. More research can be done to determine what specific types of interventions can be helpful once those at-risk youth are identified.

The success of Preventure offers providers insight into to the early signs and symptoms  of those children who are at greatest risk of addiction.  For kids with personality traits that put them at risk of addiction, learning how to manage them can potentially change the trajectory that can lead to tragedy.  Early cognitive behavioral therapy to address the underlying emotional and mental health challenges may help reduce the likelihood of addiction.