Disruptive mood dysregulation disorder

Disruptive mood dysregulation disorder (DMDD) refers to the presentation of children with persistent irritability and severe recurrent temper outbursts. Recurrent episodes of severe behavioural dyscontrol usually include verbal rages and physical aggression toward people or property. The mood is persistently angry and irritable even between temper outbursts.

According to DSM, onset must be before the age of ten years, and the diagnosis should not be applied to children that are less than six years, nor should it be made for the first time after 18 years of age. DMDD cannot coexist with oppositional defiant disorder (ODD), intermittent explosive disorder (IED), MDD, attention-deficit/ hyperactivity disorder (ADHD), conduct disorder (CD), and substance use disorders (SUD) (American Psychiatric Association, 2013).

Treatment of major depressive disorder

Multiple drug classes are available for the treatment of MDD. While newer classes of medications are usually the first line of treatment, older medications might still be chosen, depending on the subtype of MDD, the age of the patient, cost considerations, and the practitioner’s preferences. Before starting a treatment, a careful evaluation of suicide risk is necessary, including specific inquiries about suicidal thoughts, plans, means, intent, and behaviours; evaluation of current or past presence of symptoms and conditions such as psychosis, substance use, bipolar symptoms, and severe anxiety, all of which may increase the likelihood of acting on suicidal thoughts. Past and recent suicidal behaviour should be evaluated along with the current stressors and potential protective factors (e.g. presence of children at home, religious/spiritual beliefs, positive reasons for living, and a high level of social support). Family history of suicide should be carefully evaluated and given appropriate weight in treatment decisions. Impulsivity and potential for risk to others should also be assessed, including any history of violence or homicidal ideas, plans, or intentions. The patient’s risk of selfharm or harm to others should also be monitored as treatment proceeds (American Psychiatric Association, 2010).

Most antidepressants have similar rates of efficacy overall but differ in terms of side- effect profiles. Usually, the initial selection of an antidepressant medication is based on the safety, anticipated side effects, and their tolerability for the individual patient. Pharmacological properties of the medication (e.g. half-life, actions on cytochrome P450 enzymes, other drug interactions, efficacy on sleep, efficacy on anxiety), and additional factors such history of response in prior episodes, cost, and patient preference must be considered as well. For most patients, the first-line treatment is usually a selective serotonin-reuptake inhibitor, psychotherapy, or a combination of pharmacotherapy and psychotherapy (Gelenberg, 2010).

Selective serotonin reuptake inhibitors currently available include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram. A large body of literature supports the superiority of SSRIs compared with placebo, including trials conducted in primary care settings (Arroll et al., 2005). Also, in several trials, SSRIs have demonstrated comparable efficacy to the TCAs (Cipriani, 2005; Anderson, 2000; Montgomery, 2001).

Serotonin norepinephrine reuptake inhibitors (SNRIs) mirtazapine or bupropion are good choices as well. Next-step treatment recommendations are switching or augmentation, depending on patient response to the initial treatment. In general, the use of nonselective monoamine oxidase inhibitors (MAOIs) should be restricted to patients who do not respond to other treatments, given the potential for deleterious drug-drug interactions (DDIs) and the necessity for dietary restrictions (American Psychiatric Association, 2010).

Electroconvulsive therapy (ECT) should be considered as a treatment option for individuals with major depressive disorder who experience psychotic features or catatonia. Also, ECT is a first line choice for patients with an urgent need for response, such as patients at high suicide risk or those who refuse to eat. Other situations favouring ECT include the presence of co-occurring general medical conditions that preclude the use of antidepressant medications, a prior history of positive response to ECT, and patient preference (American Psychiatric Association, 2010).

Once an antidepressant medication has been initiated, the titration rate to a full therapeutic dose usually depends upon tolerability, patient’s age, co-occurring illnesses, and concomitant medications. During the acute phase of treatment, patients should be evaluated on a regular basis to assess their response and patient safety, and to identify the emergence of side effects (e.g. dizziness, blurred vision, gastrointestinal symptoms, sedation, insomnia, activation, changes in weight, and cardiovascular, neurological, anticholinergic, sexual side effects, etc.).

The starting and usual doses of the most commonly used antidepressants are reported in Table 10.1. Links to the FDA-approved prescribing information are reported in Box 10.1.

SSRIs undergo hepatic oxidative metabolism before their elimination from the body; therefore, genetic differences in oxidative metabolism can significantly impact the levels of an active drug circulating in a patient. Also, SSRIs have variable effects on hepatic microsomal enzymes and may increase or decrease the blood levels of other medications. For instance, SSRIs that strongly inhibit the CYP 2D6 isoenzyme (e.g.

Table 10.1 Doses of most commonly used antidepressants

*20 mg/day is the citalopram recommended dose for most elderly patients and patients with hepatic impairment

Box 10.1 FDA-approved prescribing information

Bupropion, FDA-approved prescribing information. Accessed on January 2016 at: http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A- Wellbutrin-Tabs-SLR028.pdf

Buproprion extended release (wellbutrin XL), FDA-approved prescribing information. Accessed on January 2016 at:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021515s023s

024lbl.pdf

Citalopram, FDA-approved prescribing information. Accessed on January 2016 at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020822s037, 021046s015lbl.pdf

Desvenlafaxine, FDA approved prescribing information. Accessed on January 2016 at: http://labeling.pfizer.com/showlabeling.aspx?id=497%20 Duloxetine, FDA approved prescribing information. Accessed on January 2016 at: http://pi.lilly.com/us/cymbalta-pi.pdf

Escitalopram, FDA approved prescribing information. Accessed on January 2016 at: http://pi.actavis.com/data_stream.asp?product_group=1907&p=pi&language=E Fluoxetine, FDA approved prescribing information. Accessed on January 2016 at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018936s091lbl.pdf Mirtazapine, FDA approved prescribing information. Accessed on January 2016 at: https://www.merck.com/product/usa/pi_circulars/r/remeron/remerontablets_ pi.pdf

Paroxetine, FDA approved prescribing information. Accessed on January 2016 at: https://www.apotex.com/us/en/products/downloads/pil/paxil_irtb_ins.pdf Paroxetine extended release, FDA approved prescribing information. Accessed on January 2016 at:

http://www.fda.gov/ohrms/dockets/ac/04/briefing/4006b1_08_paxil-label.pdf Sertraline, FDA approved prescribing information. Accessed on January 2016 at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019839s070, 020990s032lbl.pdf

Trazodone OAD Contramid, FDA approved prescribing information. Accessed on January 2016 at:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022411lbl.pdf Venlafaxine, FDA approved prescribing information. Accessed on January 2016 at: http://labeling.pfizer.com/showlabeling.aspx?ID=100

paroxetine, fluoxetine) may reduce the metabolism of tamoxifen to its active metabolite is reduced, resulting in a decrease in its efficacy in preventing breast cancer relapse (Stearns, 2003; Jin, 2005; Desmarais, 2009). This effect is also observed for other antidepressants, such as bupropion (Desmarais, 2009).

• [1] 10 mg/day is the escitalopram recommended dose for most elderly patients and patients with hepaticimpairment
• [2] The limit of 150 mg in a single dose of non-XL bupropion should never be exceeded