In the past few decades, there has been a rise in mental health disorders in children and adolescents, as reflected by a report on the trends in mental illness in the past 10 years (1994–2024) published by the Fundación de Atención de Niños y Adolescentes en Riesgo (ANAR, Foundation for the Care of At-Risk Children and Adolescents).1 Parallel to this, there has been an increasing trend in the prescribing of psychotropic medication to children and youth.2 It is important to be aware that the pharmacokinetics and pharmacodynamics of these drugs in the pediatric population differ from those in adults, in addition to the fact that, in the case of the former, they act on brains that are still developing. Although at present it is possible to prescribe psychotropic drugs to pediatric patients in a scientifically rigorous manner, based on their efficacy and low risk of adverse events, they are frequently used off-label.3 However, the general rule is to follow the guidelines approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In everyday practice, the management of mental health conditions in the pediatric population is not restricted to the scope of practice of psychiatrists and psychologists, and pediatricians play a key role in their detection, diagnosis and treatment. Therefore, it is important that they know the most commonly used psychotropic drugs, their indications, and their side effects, always taking into account that pharmacotherapy must be part of a multimodal treatment plan that also includes educational and psychological intervention. This narrative review highlights the practical aspects of the psychotropic drugs most commonly prescribed in the pediatric population.

The evidence indicates that the effectiveness and safety of pharmacological treatment for attention deficit hyperactivity disorder (ADHD) are very high. Furthermore, these drugs do not cause dependence or predispose patients to the use of addictive substances when used as prescribed (therapeutic dose and oral administration). Their use is necessary in a high percentage of patients with moderate or severe ADHD, especially from age 6 years onwards. Two distinct groups of drugs used for treatment of ADHD are currently available in Spain: stimulant medications (methylphenidate and lisdexamfetamine dimesylate) and nonstimulant medications (atomoxetine [ATX] and guanfacine). The use of any of these drugs in children younger than 6 years is not contemplated in the summary of product characteristics.

The use of antipsychotics in patients aged less than 18 years has grown steadily in recent years.21 They are indicated to improve disorganized thinking and behavioral symptoms (such as those seen in psychotic spectrum disorders). They reduce the activation of dopaminergic circuits, so they are first-line drugs for psychosis, mania, bipolar disorder and tics. They are also the treatment of choice for severe conduct disorders when other measures have been ineffective.22

Their mechanism of action involves different interactions with dopaminergic receptors, reducing their activation, as they are antagonists or partial antagonists of D2-type receptors. Some of them also act on serotonergic and muscarinic receptors. The antipsychotics are divided into typical/classic antipsychotics and atypical/second-generation antipsychotics, the latter of which are better tolerated. The indications are similar for all of them, as the different drugs chiefly differ in the severity of the adverse effects. Table 4 presents the most commonly used antipsychotic medications, including information on the available presentations and their dosage. The incidence of adverse effects is generally low, since the doses used in children and adolescents tend to be low. Table 5 summarizes their main adverse effects and their management.23

Typical antipsychotics are rarely used in individuals aged less than 18 years due to their frequent and severe side effects. Among those approved by the FDA and the EMA, the most widely used are haloperidol and chlorpromazine. They are administered to treat episodes of psychomotor agitation, intramuscularly, when administration of an alternative oral drug is not possible, and to treat acute psychotic episodes or for ongoing treatment of severe conduct disorders, administered orally, when other treatment options have been ineffective.

The adverse effects of atypical antipsychotics are similar to those of typical antipsychotics, but less frequent and severe. The strongest evidence of their effectiveness concerns their use for psychotic disorders, such as schizophrenia, and autism spectrum disorder, improving target symptoms and comorbid behavioral disorders. Risperidone and aripiprazole are approved by the FDA and EMA for use in children aged six years and older, although they are often used at younger ages (off-label).

Risperidone is the most widely used and extensively investigated.24 It is considered the first-line drug when pharmacotherapy with an antipsychotic is required in a child or adolescent. Aripiprazole is also considered a first-line drug and is a partial dopaminergic agonist, so it is less potent than other atypical neuroleptics, although its side effects tend to be less pronounced.25

Although prescribed less frequently, there are other atypical antipsychotics that may be useful approved by the FDA and the EMA from preadolescence, such as paliperidone, olanzapine, quetiapine and lurasidone.

Selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice for treating depression. Their mechanism of action is based on increasing serotonergic transmission by blocking the serotonin reuptake transporters (5-HT receptors). They have an antidepressant and anxiolytic effect, which is why they are indicated as the first-line drug in the treatment of anxiety and mood disorders.26 In recent years, other antidepressants with different mechanisms of action have been introduced in the pediatric population, such as dual serotonin-norepinephrine reuptake inhibitors, although these should be considered a second-line option in cases in which SSRIs have not been effective. Finally, tricyclic antidepressants can also be used, although they are less desirable due to their adverse effects.27

Some key aspects to consider in clinical practice are:

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  The starting dose should be half the minimum recommended dose, increasing to therapeutic doses after seven to 14 days to prevent the development of adverse effects.

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  The onset of action occurs four to five weeks after starting treatment. If there is no therapeutic effect, the diagnosis, the presence of comorbidities, or any other factors that may interfere with response, including lack of adherence, must be reconsidered.

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  Once clinical stability is achieved, treatment should be maintained for a prolonged period (10–12 months) before considering its gradual withdrawal.

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  Studies on childhood depression have found high rates of response to placebo. Therefore, more studies using SSRIs and other antidepressants are needed to better evaluate their long-term efficacy and safety.28

Table 6 presents the antidepressants used in the pediatric population, with the starting dose, therapeutic range, and minimum age to start treatment based on the FDA and EMA recommendations.

In children, the adverse effects of SSRIs tend to be mild and transient, especially in the early weeks of treatment.29 The most frequent adverse effects are gastrointestinal symptoms, such as nausea, vomiting or abdominal pain, headache, and sleep disturbances such as nightmares, insomnia or hypersomnia. Rare adverse events include impulsivity, agitation or behavioral disinhibition.

In 2004, the FDA mandated a black-box warning regarding the increased risk of suicidal ideation and behavior in adolescents treated with antidepressants. However, an expansion of the warning in 2007 recognized that depression symptoms themselves are associated with suicidality, so that the latter may not be attributable to antidepressant use.

In children and adolescents, benzodiazepines should be used sparingly and only as a temporizing measure while SSRIs and psychotherapy take effect. They are not indicated for long-term use as hypnotic agents. In children, they are frequently prescribed to improve anxiety in the short term, but there is no evidence supporting their long-term efficacy.30 Although they can be prescribed from age 2 years, they should be avoided before age 9 years. They are generally included in the last step of treatment protocols, as they act on GABA receptors. In adults, the GABAergic effects of benzodiazepines are sedating and directly anxiolytic. However, the maturation of neurons that express GABA receptors is not complete until adolescence. In consequence, the use of benzodiazepines in children can cause paradoxical reactions and is associated with a higher incidence of adverse events. Their use in individuals aged less than 18 years has not been approved by either the FDA or the EMA.31

In clinical practice, they may be used off-label in cases of acute, severe anxiety for a period lasting less than four weeks, in combination with other anxiolytic agents or psychological therapies that usually require several weeks to take effect, at which time the benzodiazepine should be tapered off slowly until its complete cessation.

The use of long-acting benzodiazepines is preferred, as it decreases the probability of adverse effects. The most widely used ones are clorazepate (dose: 2.5−10 mg) and diazepam (dose: 2.5−5 mg), administered as a single dose in the morning. If the patient experiences somnolence, it can be split into several doses. If anxiety increases between two doses, an extra dose can be given exceptionally. Treatment should be initiated at a low dose, increasing it every three to seven days if symptoms persist. The simultaneous use of more than one type of benzodiazepine is not recommended. Once symptom control is achieved, the drug should be tapered off slowly. Short-acting benzodiazepines should be reserved for special situations, with treatment consisting of a single dose. Midazolam can be used in children aged more than 1 month for anxiolysis before medical or surgical procedures at a dose of 0.25–0.5 mg/kg (maximum dose, 20 mg), with administration 30 min before the intervention.32

It is important to be watchful for the development of tolerance, dependence and side effects. The most frequent adverse events are somnolence, memory and attention problems, behavioral disinhibition, hypotension and dizziness, and constipation.

They include anticonvulsants, lithium and antipsychotics. They are indicated for bipolar disorder and for symptomatic treatment of impulsivity, behavior disorders or aggression.33Table 7 presents the starting doses, therapeutic ranges and minimum age for mood stabilizers.

Melatonin is a neurohormone used as the first-line drug for insomnia in children and adolescents in the framework of a comprehensive plan that includes assessment of sleep characteristics and nonpharmacological measures.36

The estimated dose is 1–3 mg for infants and preschoolers, and 2–5 mg for older children and adolescents. Melatonin should be administered 30−60 min before bedtime.37 It reduces sleep latency.

There is also extended-release melatonin, which has been found effective in reducing sleep latency and the frequency of nighttime awakenings in children with neurodevelopmental disorders.

In the past few years, there have been significant advances in psychopharmacology for children and adolescents, despite the limitations of the current evidence. More studies are required to analyze and optimize key aspects, such as the indications for age, long-term safety and effectiveness, or weight-based dose titration, among others.

The reason that knowing the main pharmacological strategies for the management of mental health disorders in children is important is twofold. On one hand, the increase in the prevalence of conduct, neurodevelopmental and mood disorders,38 and, on the other, the increase in the prescribing of psychotropic drugs in the pediatric population as more evidence on their utility becomes available.39,40

The use of psychotropic drugs in the pediatric population should be integrated in a comprehensive treatment plan including both pharmacological and nonpharmacological interventions and tailored to the specific needs of the patient. This approach requires thorough planning, clear treatment goals, and periodic reassessments to adjust the treatment strategy based on the clinical response.

It is essential to be familiar with the main drug groups, their mechanisms of action and their side effects, especially in the pediatric population, in which dose titration and monitoring are crucial due to the variation in response to treatment.

P.J. Rodríguez Hernández has received continuing medical education (CME) funding from Angelini Pharma, Exeltis Healthcare, Recordati, Rovi, Rubio, and Takeda; research support from Fundación Médicos de Tenerife; and royalties for books or publications from Editorial Médica Panamericana.

G. Ochando Perales has received continuing medical education funding from Exeltis, Rubio, and Takeda; a research grant from the Colegio de Médicos de Valencia; and royalties for books or publications from Editorial Médica Panamericana.

C. Soutullo Esperón has received research support from the Texas Child Mental Health Care Consortium-SB 11 (Texas Youth Depression and Suicide Research Network), Innosphere, the John S. Dunn Foundation, the Vivian L. Smith Foundation, and The Favrot Fund (2023–2025); serves as consultant/advisory board member for NeuroTech Solutions, Innosphere, Limbix/Big Health, and Medice; has delivered CME lectures for Bial, Medice, Cuquerella Medical Communications, and Tecnofarma; and has received royalties for books or publications from Editorial Médica Panamericana.

R. Calvo Escalona has received research funding from Instituto de Salud Carlos III, IMI-2 EU, Acadia, and Roche; and has received honoraria for CME lectures and educational materials from Viatris and Neuraxpharm.