Front line treatments are well known, and include:

1. various forms and types of psychotherapies (individual and/or family, DBT, IPT, etc.),
2. medications such as the selective serotonin re-uptake inhibitors (SSRIs), selective norepinephrine uptake inhibitors (SNRIs), and others, and
3. various supportive interventions, such as school supports and increasing social activities.

Each of the above interventions have established benefits (and limitations) but the general consensus is that multi-modal interventions, where indicated and as feasible, are appropriate approaches in treatment of depressive (and most other) disorders.   When depression presents with mild to modest levels of symptoms, skillful evaluation and psychotherapeutic interventions are typically recommended as the first of these first line therapies to be suggested.

When presenting symptoms are more profound or when psychotherapy and supportive services are not having desired impact, consideration should be given to the initiation of psychopharmacologic intervention(s) in conjunction with ongoing outpatient services.  When presentations include concerns about potential harm, referral to a higher level of care need to be considered.

For a review of these basics, feel free to search our SmartCare newsletter library at www.vistahillccyp.org/ or reach out to the SmartCare provide line at 858 880-6405.

Supplemental treatment interventions of note:   Following is a brief discussion of some other complementary and/or alternative interventions that have evolving, but generally favorable (and, at worst, no major negative) evidence of potential efficacy that can be considered for implementation for patients and/or parents seeking to utilize them as supplemental interventions.

• Vitamin D deficiency is a known risk factor for depression but use of Vitamin D in depressed patients has generally proved challenging to affirm as of definitive benefit across all patients and blood levels can vary considerably across the population.  This said, multiple studies have looked at the role of vitamin for adolescents with depression (Libuda et al., 2020; Focker et al., 2018), and Libuda et al. found in a randomized control trial that youth with Vitamin D deficiency and depression treated with 2640 IU of Vit D3 per day had significant improvement in parental ratings of depressive symptoms.  More studies are needed, but this data suggests that offering supplemental treatment for youth with suspected vitamin D deficiency with depression may be worthwhile.
• Exercise, Yoga and Meditation (Cullen et al., 2019), not surprisingly, is generally believed to have a role in the augmenting treatment of depression, and preliminary data is positive. More research is certainly required, but these elements fit in well with the theoretical underpinnings of cognitive behavioral therapy, and current perspectives of health and wellness. It makes sense to encourage adolescents to take advantage of opportunities for the activities.
• Fish Oil, or Omega-3 fatty acids are also being studied. While there is not strong evidence for the role of Fish Oil as a specific treatment, there is ongoing investigation (Haberling et al., 2019).  We expect there to be more interest and information in this in the upcoming years.

Altering Diet, with attention to specific supplements may play a role in the future (Cullen et al., 2019). Currently data is preliminary

Cullen, K. R., Padilla, L. E., Papke, V. N., & Klimes-Dougan, B. (2019). New Somatic Treatments for Child and Adolescent Depression. Current treatment options in psychiatry, 6(4), 380–400. https://doi.org/10.1007/s40501-019-00194-8

Häberling, I., Berger, G., Schmeck, K., Held, U., & Walitza, S. (2019). Omega-3 Fatty Acids as a Treatment for Pediatric Depression. A Phase III, 36 Weeks, Multi-Center, Double-Blind, Placebo-Controlled Randomized Superiority Study. Frontiers in psychiatry, 10, 863. https://doi.org/10.3389/fpsyt.2019.00863

Libuda L, Timmesfeld N, Antel J, Hirtz R, Bauer J, Führer D, Zwanziger D, Öztürk D, Langenbach G, Hahn D, Ring S, Peters T, Hinney A, Bühlmeier J, Hebebrand J, Grasemann C, Föcker M. Effect of vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients: results of a randomized controlled trial. Eur J Nutr. 2020 Dec;59(8):3415-3424. doi: 10.1007/s00394-020-02176-6. Epub 2020 Feb 27. PMID: 32108263; PMCID: PMC7669774.

Föcker, M., Antel, J., Grasemann, C., Führer, D., Timmesfeld, N., Öztürk, D., Peters, T., Hinney, A., Hebebrand, J., & Libuda, L. (2018). Effect of an vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients – a randomized controlled trial: study protocol. BMC psychiatry, 18(1), 57. https://doi.org/10.1186/s12888-018-1637-7

Treatment options include therapy or a combination of therapy and medication:

• For patients with mild-moderate symptoms, a therapy approach is preferred, with the option incorporate medication if the therapy is not effective.
• For patients with moderate-severe symptoms with significant impairment in daily functioning, it may be warranted to consider starting with a combination of medication and therapy.

The key is that therapy is the important component to treatment of anxiety disorders in pediatrics, with medication used as an adjunctive treatment when needed. Therapy to address anxiety can easily be tailored to work with very young patients and is very effective. Types of therapy used include: cognitive behavioral therapy, exposure response prevention therapy, and relaxation techniques, among others.

Medications used to treat anxiety fall into two general categories: medications that treat the underlying anxiety and prevent future symptomatology and medications that treat acute symptoms, such as a panic attack. Medications in the first category include the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazipine, and buspirone.  The SSRIs are the first line agents. This class includes: fluoxetine, citalopram, escitalopram, sertraline, fluvoxamine, and paroxetine.  Although prompt relief may result, just as with treating depression, the medication may take 4-6 weeks to have full impact, so patience is important.  Also of note, often a higher dose may be needed to fully treat anxiety symptoms as compared to depressive symptoms.

The motto to “start low and go slow” remains relevant to limit activation and thereby increase anxiety 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 q-day for one week then 10 mg q-day for 1 week then 20 mg q-day 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 are dose related and will 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 appropriate 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 prescribing a medication, it is standard practice to first use an SSRI.  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 mirtazapine, but consultation or referral to psychiatry would be advised in such situations. If there is some benefit from the SSRI, one could consider augmentation with mirtazapine or buspirone. The primary side effects to be concerned with mirtazapine 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.

Benzodiazepines, are rarely used in this population. Pediatric patients can have a paradoxical reaction to them 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, which is not associated with dependence. Side effects include: sleepiness, dizziness, and dry mouth.

When feasible, the use of rating scales can help in these efforts by documenting severity and monitoring clinical progress.   A good tool to review, the SCARED, is accessible at. http://www.pediatricbipolar.pitt.edu/content.asp?id=2333#3304 and a broader array of tools is listed at the following website http://www2.massgeneral.org/schoolpsychiatry/screening_anxiety.asp

ADHD is a neurodevelopmental disorder characterized by impairing hyperactivity, impulsivity and inattention, and persistent irritability and out of proportion temper outbursts are not typically seen with ADHD alone. Children with DMDD can have some challenges with hyperactivity and impulsivity but with the underlying irritability and angry mood present as well. A child can present with both diagnoses concurrently.

Children with ODD exhibit a pattern of anger-guided disobedience and defiant behavior toward authority figures. Clinically it is observed that ODD stems from learned behavior and/or parenting challenges, whereas DMDD seems to have a more organic process. While some of the symptoms of ODD may overlap with the criteria for DMDD, the symptom threshold for DMDD is higher since it is considered to be a more severe condition. Most children with DMDD also meet criteria for ODD and about 15% of children with ODD also meet criteria for DMDD. Therefore it is recommended that children who meet the criteria for both ODD and DMDD should only be diagnosed with DMDD.

Children with bipolar disorder can have symptoms that are similar to those with DMDD. The primary difference is that the mood symptoms seen in bipolar disorder are episodic, which is not the case in DMDD. If the irritability is episodic and there are also distinct periods of depression, a child is more likely to have bipolar disorder. A diagnosis of pediatric bipolar disorder would rule out DMDD. It has been shown that children who present with chronic, rather than episodic, irritability, who may have been given a diagnosis of bipolar disorder for lack of a better fit, are at greater risk of developing depression and generalized anxiety rather than life-long bipolar disorder. This was additional information to support the idea that a different diagnosis was needed to describe children with clinically impairing chronic irritability.

Because DMDD is such a new diagnosis, research is being conducted to determine the is being conducted to determine the best treatment. Medication, including SSRIs and stimulants, psychotherapy and a combination of the two are being used. The differential diagnosis includes: ADHD, ODD, bipolar disorder, major depression, substance abuse and ASD. It is important to assess for co-morbid symptoms, underlying factors and antecedents/triggers to help make an accurate diagnosis.

Pharmacological options include benzodiazepines, non-benzodiazepines, antidepressants and antihistamines. There is limited evidence on their long-term safety particularly with cognitively-impaired older adults. For this reason, it is important to use these medications with caution, for the shortest period of time as needed, and to follow the motto “start low and go slow”. Benzodiazepines are commonly used, but they have little effect on the sleep maintenance problems that are most commonly seen in older adults with dementia. In addition, they can have problematic side effects, including sedation, confusion, anterograde amnesia, and rebound insomnia, which can make the behavioral disturbance seen with dementia worse. The newer generation non-benzodiazepines have shorter half-lives and fewer side effects, but there is limited data on their use in older patients with dementia.

Antidepressants, including Trazodone, the SSRIs and Remeron, are sometimes used to help with sleep problems, in some cases to take advantage of their side effect of sedation and in other cases because there is concern about co-morbid depression. Trazodone has been found in small studies to be helpful short-term with improving total sleep time and sleep efficiency. Antihistamines are commonly used in this situation, partly because of the availability over-the-counter, but there are side effect concerns, including sedation, cognitive impairment, and anticholinergic responses. Because of these side effect risks, they should be avoided as first-like agents in older patients. Supplemental melatonin has not been found to be helpful as a stand-alone treatment for insomnia in patients with dementia in studies, but ramelteon, a melatonin agonist, has been shown some promising results in general studies, to improve sleep efficiency and increase total sleep time. In addition, it is not associated with side effects that are seen with other medications used for sleep disturbance, like cognitive impairment and daytime sleepiness. It would be helpful for more studies to be done with this agent in older patients.

It is our hope that this article has been helpful in addressing the common issue of sleep disturbance in patients with dementia, to begin thinking about how to determine the cause and the best treatment approach.

Reference: Current Treatments for Sleep Disturbances in Individuals with Dementia. Cynthia L Deschenes, MSN, CCRN and Susan M. McCurry, PhD. Curr Psychiatry Rep 2009, Feb.