Table 1.
Summary of review findings.
| Comorbid Condition | Main Recommendations |
|---|---|
| ADHD | MPH is greatly effective in improving ADHD core symptoms and emotional dysregulation with non-significant adverse effects, low risk of (hypo)manic switch and possible beneficial effects on suicidality |
| ATX is effective in improving ADHD core symptoms with ongoing mood stabilizers (e.g., with Valproic Acid), but has the potential but still debated risk of inducing (hypo)manic switches and suicidality | |
| A two-step treatment approach is recommended with mood stabilizers prescription preceding the treatment of ADHD symptoms to prevent mood destabilization, especially in BD type 1 | |
| MPH should be considered as first-line treatment option, followed by ATX when MPH is ineffective or contraindicated; other stimulants can be also effective after mood stabilization | |
| ADHD medications may be contraindicated in youths with comorbid substance use disorder, especially when ADHD symptoms are simulated or exaggerated to obtain stimulants for diversion or abuse | |
| DBD | No medications are currently approved in US for CD, while Risperidone is approved in Europe for aggression; evidence favors antipsychotics over mood stabilizers for treating mania |
| Lithium may be effective on aggression in CD, and the successful treatment of BD can mitigate CD symptoms, though comorbid CD is a predictor of non-response to both Lithium and Valproic Acid | |
| SGAs show similar efficacy in treating mania and aggression, but Quetiapine is more effective on anxiety, depression, and suicidality, while metabolic changes are more evident with Risperidone | |
| SUD | Lithium is the only treatment with positive results in a randomized-controlled study of adolescents; Valproic Acid add-on may be considered for AUD, based on adult trials |
| Quetiapine and Aripiprazole showed limited benefits in adult AUD; Citicoline and Gabapentin are promising options, respectively, for cocaine dependence and CUD | |
| Prevention of SUD should be the focus of treatment in patients with multiple risk factors; in high-risk patients a mood stabilizer may be introduced before the onset of full-blown BD | |
| ASD | Pharmacological treatment does not address ASD core symptoms but rather targets challenging behaviors; the presence of comorbidity does not impact the rate of response to irritability |
| Lithium may be effective for mood swings, (hypo)manic symptoms, impulsivity, and irritability, while VPA is the anticonvulsant with the largest evidence in the comorbid condition | |
| Risperidone and Aripiprazole are currently approved for treating irritability and aggression and are particularly indicated when impulsive aggression is prominent | |
| Mood stabilizers may be preferable especially when aggression is limited; antipsychotics should be used at the lowest effective dose and for the strictly necessary periods to minimize adverse effects | |
| Anxiety Disorders | The use of antidepressants is supported, though with associated specific increased risk of (hypo)mania, which requires closely monitoring of irritability and suicidality |
| Mood stabilizers with anxiolytic properties should be first considered in youths (Valproic Acid, Gabapentin) | |
| In the short-term Quetiapine and Olanzapine may exhibit greater beneficial effects on anxiety compared to antiepileptics | |
| OCD | Antidepressants should be given at the lowest effective dose with careful monitoring of (hypo)manic symptoms due to high rates of switches, especially with Clomipramine |
| Mood stabilizers, even in combination (e.g., Lithium and antiepileptics), are required in virtually all patients; BD should be the primary focus of pharmacological treatment | |
| SGAs are required in case of complex comorbidity, high severity, and refractoriness in more than half of patients; Olanzapine, Risperidone, Aripiprazole and Quetiapine are available treatment options | |
| A combination of mood stabilizers, antidepressants and SGAs may be indicated for selected patients | |
| ED | Stabilization of affective symptoms may have a beneficial impact on eating behaviors, but the choice of effective approaches for each syndrome should consider avoiding iatrogenic effects on the other |
| Antidepressants (i.e., Fluoxetine) should be given with caution due to increased risk of (hypo)manic switch, affective instability, impulsivity, and suicidality, even when prescribed with mood stabilizers | |
| Among mood stabilizers, Lithium may be effective in AN; Topiramate and Zonisamide have shown some efficacy for treating BED, but their use in BD is controversial | |
| SGAs should be avoided for their disruptive effects on hunger regulation, increased weight gain and dysfunctional eating behaviors, along with negative metabolic and cardiovascular effects |