Approach
The following treatment recommendations are based on published treatment guidelines.[66][67][85][86]
It is crucial to make an accurate diagnosis, based on a comprehensive assessment and review of the history, with input from multiple sources. The safety of the child and others, and the duration and severity of depression, need to be evaluated carefully to help determine the appropriate level of care and treatment modality. Ongoing assessments of safety, symptoms, and treatment response are important in limiting adverse events and in optimising and guiding the treatment approach.
Confidentiality should be discussed with the patient and his or her family, including the limits of confidentiality (e.g., the need to inform parents or legal authorities if there is an imminent risk of harm to the patient or to others [in keeping with clinicians’ local legal frameworks]).[64]
Generalist versus specialist care
Depression in children and adolescents presents with a broad phenotype and psychosocial complexity. It is important for physicians to appreciate the scope of practice that is required to safely and effectively manage the care of a young person with depression. Subsequent sections about treatment will specifically emphasise which interventions should ideally or only be provided under specialist provider care, and the remainder of the text will apply to generalist care.
Generalists include general practitioners, paediatricians, and general adult psychiatrists with limited experience of children and youth. Specialists include accredited child and youth psychiatrists and general adult psychiatrists with extensive experience of children and youth.
Generalists manage mild to moderate severity with or without simple comorbidity, and their treatments are well supported by evidence. Specialists manage moderate to severe illness, often with complex comorbidity. Evidence for treatment may be lacking.
Phases of treatment
The treatment of depression can be divided into 3 phases.
Acute: lasting for 6 to 12 weeks; the goal of this phase is to achieve remission (i.e., for the patient to become asymptomatic or to have minimal symptoms only).
Continuation: immediately follows the acute phase, and lasts for 6 to 12 months (ideally 6 months for first episode and 12 months for recurrent episode); the goal of this phase is to prevent relapse. The same treatment regimen that was effective for acute treatment should be continued. Without continuing effective treatment, relapse rates are very high, as demonstrated in both psychotherapy and medication studies.[87] In the case of fluoxetine, even with continuation of treatment, many children and adolescents relapse. It has also been found that adding 6 months of continuation-phase cognitive behavioural therapy (CBT) after acute CBT significantly lowered relapse rates compared with historical controls (6% vs. 50%).[88]
Maintenance: follows the continuation phase in some people; 1 to 2 years of the maintenance treatment may be recommended for young people at risk for recurrence (e.g., those with high genetic loading, chronic depression, multiple episodes, and severe episodes). One small paediatric depression maintenance study has been reported.[89] Although a larger study is needed, maintenance treatment is recommended by treatment guidelines.
Establishing a good therapeutic alliance with both the child and the parents, providing psychoeducation, and including family in the treatment decision-making process may improve adherence and promote positive outcomes throughout the treatment phases. As suicidal thoughts are a symptom of the disorder, and entail increased safety risk for the patient, suicidal thoughts should be monitored regularly during the assessment and treatment phases, and assessed at each clinical encounter.[68]
Urgent measures for children at risk of harm to themselves or others
Suicidal behaviours such as self-harm and suicide attempts are common in children and adolescents with depression. The most important aspect of care is for the clinician to be aware of the extent of these behaviours in the patient. At the initial consultation and follow-up appointments, the patient should be asked about self-harm; troubleshoot about the reasons for it that may be modifiable, and ensure that the patient has not made an interim suicide or self-harm attempt.
It is recommended that health care professionals screen adolescents for suicidal ideation without carers present, given that young people may be reluctant to report suicidal ideation in the company of carers. However, it is important to discuss both the importance of and the limitations of confidentiality with patients and their families before seeing the patient alone.[68] The limits of confidentiality include scenarios when breaching confidentiality is necessary to protect patient and/or public safety. This can be a challenging area and requires clinical judgment, as well as knowledge of local/state/national legal frameworks; external advice from an ethics or risk management consultant may be beneficial. It is important to note that recent or active suicidal ideation (including suicide attempts) must always be communicated to a responsible adult in order to protect the minor from harm, and to involve the carer in necessary treatment.[68] Ideally, and if at all possible, this should be done with the consent of the patient.
Children and adolescents experiencing suicidal ideation, particularly those who have suicidal ideation and a history of suicide attempts, require safety planning.[68] Safety planning is an intervention carried out in collaboration between the patient and a health care professional, for example, therapist or care manager, that encompasses helping the patient identify their risk factors for suicidal ideation as well as a series of supports that they can draw on to reduce their risk of self-harm.[68] Part of the safety plan involves helping the patient be aware of local crisis support services and ideally would involve carers in its development.
Children and adolescents who are depressed with severe suicidality and without being able to maintain safety, or with significant psychosis, require urgent referral to the emergency department. Hospitalisation may be necessary to:[90]
Carry out an urgent mental healthcare assessment
Ensure safety for the patient and/or for others
Stabilise the patient.
See: Suicide risk mitigation.
Initial step in all patients: brief active monitoring
For mild or brief uncomplicated depression, a brief period of up to 6 weeks of active monitoring, with supportive care including psychoeducation for the child and parents, may be appropriate.[67][85][86][91] Mild depression often resolves with non-specific treatment. It may be necessary to cut the monitoring period short if symptoms are severe or worsen.
If the depression becomes severe, or suicidality or psychosis develops, immediate active treatment and higher levels of care (e.g., inpatient treatment) may be required.
A lifestyle assessment and recommendations for changes in diet and exercise may facilitate treatment and achieve better outcomes. There is growing evidence in support of the use of physical exercise to prevent and treat depressive disorders. Several controlled studies have demonstrated that exercise has an efficacy comparable with antidepressant therapy, and superior efficacy compared with placebo, in reducing depressive symptoms in adults.[92] One study indicated that regular exercise significantly reduced the risk of developing dysthymia in adults.[93] A meta-analysis of randomised controlled trials of exercise (4 trials, 159 participants) confirmed previous reviews by finding a medium-sized treatment effect (effect size -0.59, 95% CI -1.08 to -0.10) favouring exercise, but the investigators cautioned there was a high risk of bias in the included studies.[94] Another meta-analysis that included both randomised and non-randomised trials of exercise (10 trials, 431 participants) found a small- to medium-sized effect in reducing symptoms (effect size -0.49, 95% CI -0.71 to -0.24), but again the authors cautioned that the quality of included studies was low.[95]
Usually no further therapy is required, apart from the management of comorbid disorders and specific resistant individual symptoms, unless the depression increases in severity or symptoms persist.
Adjunctive treatment
Typically, adjunctive medications are instituted to manage symptoms associated with mild depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. One important issue is the duration of treatment. Because some depressive symptoms may take a long time to resolve, certain patients may need adjunctive medications early on during the acute treatment phase.
For psychotic depression or agitation, an atypical antipsychotic medication may be used concomitantly with an antidepressant. This would be necessary only if the antidepressant therapy was not controlling these symptoms adequately. For mild and low-risk psychotic symptoms or agitation an antidepressant may be sufficient, because the psychotic symptoms may resolve as depression improves.
Some of these drugs are considered off-label in some countries and are only to be prescribed by a specialist experienced in the treatment of paediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.[66][67][85]
Comorbid disorders
This is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).
Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96] Antidepressants may not sufficiently resolve insomnia. Behavioural interventions are the mainstay of treatment. In older children and adolescents, cognitive behavioural therapy for insomnia (CBT-I) may be considered, as in adults. Specific principles of behavioural interventions in this group include:
Education on healthy sleep practices, e.g., a regular sleep-wake cycle, and guidance what constitutes a developmentally appropriate amount of sleep
Avoidance of electronic devices with light-emitting screens at least one hour before bedtime
Advice to use the bed for sleep only, and to get out of bed if unable to fall asleep
Relaxation techniques
Occasionally, medication in combination with behavioural therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioural interventions alone. Note that prescribing is considered off-label in most parts of the world, the evidence base in children is very limited, and there is wide variation in prescribing geographically. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a paediatric sleep clinic or other specialist setting.
Mild depression
For mild depression that does not respond to active monitoring, a course of specific evidence-based psychotherapy, such as CBT (including digital CBT) or interpersonal psychotherapy (IPT), if available and appropriate, may be used.[66][67][97][98] CBT has also been shown to have long-term effects on prevention of depression onset.[99] In the UK, the National Institute for Health and Care Excellence guidelines recommend the consideration of attachment-based family therapy for children with depression continuing after a period of watchful waiting.[67]
Moderate or severe depression
Specific psychotherapies or selective serotonin-reuptake inhibitors (SSRIs), or a combination, may be used for children and young people with depression of moderate or greater severity as first-line treatment.[100]
US guidelines recommend any of the following approaches for young people with depression of moderate or greater severity:[64][66][85]
Specific psychotherapies (e.g., CBT, IPT, dialectical behavioural therapy)
SSRI medication
A combination of specific psychotherapy and SSRI therapy
Switching drugs or combination pharmacotherapy if there has been inadequate response.
UK guidelines recommend an initial trial of psychotherapy for all young people with depression of moderate or greater severity. Antidepressants are recommended only in combination with psychotherapy and generally after a trial of psychotherapy; however, combined therapy with fluoxetine and psychotherapy may be considered for initial treatment of moderate to severe depression in young people aged 12 to 18 years.[67] The distinction between these national recommendations is that US guidelines include SSRI monotherapy as first-line treatment for moderate to severe depression.
Studies to support this recommendation include one randomised controlled trial of moderately to severely depressed adolescents in which CBT plus SSRI was no more effective than SSRI alone.[101] There was no increase in disinhibition, irritability, and violence from baseline with either treatment.[101] Time to response is faster with fluoxetine than with psychological therapy, but suicide-related behaviours are also more common.[102]
The importance of concurrent or first-line psychotherapy is supported by long-term results and safety outcomes. Combination therapy may decrease suicidal ideation more than medication alone.[103] In a meta-analysis of combined medication and psychotherapy versus medication alone, there was greater improvement in global functioning with combination treatment, but no difference was reported between the groups on depressive symptom reduction.[104]
In summary, considering both short- and long-term evidence of relative benefits of monotherapy and combination therapy for moderate to severe depression, it is reasonable to consider monotherapy with an SSRI or specific psychotherapy as the initial approach, and, if there is an inadequate response, treatment could be augmented and continued with combined SSRI and psychotherapy. The SSRI fluoxetine is typically the treatment of first choice based on meta-analysis data, although note that treatment effects may vary between individuals, and so individualised risk:benefit analysis is required when selecting an SSRI.[105][106][107][108] In particular, fluoxetine is preferable over other SSRIs when time to remission is a high priority, and can be complemented by regular risk assessment in regards to suicidality by any professional. Psychological therapy is the treatment of first choice when maintaining safety is a high priority. This is salient when a young person with major depressive disorder has prominent suicide ideation, or has engaged in self-harm.
SSRIs: general considerations
SSRIs are the drug of choice, if a drug is required, and are often used after non-pharmacological steps have failed.
[ 
]
A meta-analysis including 36 trials (6778 participants) found that SSRIs seem to be more beneficial than placebo for treating children and adolescents with depression, but that the effect size was small. The results suggest that, for children and adolescents with depression, the placebo effect plays a significant role in the efficacy of SSRIs.[109] The US Food and Drug Administration (FDA) issued a black box warning on suicidality associated with paediatric use of antidepressants in 2004.[110]
When discussing the use of an SSRI for treatment of depression, it is important to set realistic expectations for the child and carer. Not all children with depression will respond to an SSRI. Response, if positive, is subtle and gradual and requires physician monitoring. Not all depressive symptoms will respond to an SSRI; thus, it is important to consider adjunct interventions, mostly environmental, for those symptoms (e.g., sleep and pleasurable activity scheduling, appropriate nutrition and exercise, and classroom accommodations).
In addition, when starting medication, ensure the carer appreciates the importance of monitoring the administration and safe-keeping of medication. Many children struggle with compliance and sometimes misuse or attempt to overdose on medications. Deciding on safe-keeping of the medication in the home or the use of small-dose packaging is essential in this regard.
Fluoxetine
The benefits of fluoxetine are supported by a strong body of meta-analysis data in both children and adolescents.[105][106][107][108]
Doses may be increased incrementally after initial starting regimen if there is not sufficient improvement (<50% of reduction in depression severity) of depressive symptoms.[111] Adolescents may be more likely to need an increase to a higher dose than children.[112]
Fluoxetine may have greater and more rapid efficacy in premenstrual dysphoric disorder.[113]
Fluoxetine has the longest half-life of the recommended SSRIs (4-6 days in adults) and is a potent inhibitor of cytochrome P450 enzyme 2D6 and 2C19. When concomitant medications that are metabolised by these enzymes are used, a reduced dose may be considered.
There is evidence to suggest that fluoxetine during the first trimester of pregnancy may be associated with a slightly increased risk of congenital heart malformations in the baby. In consideration of this finding, the physician should also take into account the established conferred risk to the fetus and newborn when the adolescent mother is depressed.[114]
Escitalopram
May be used as a first-choice antidepressant for adolescents, but not children. One trial that included children and adolescents demonstrated positive results for escitalopram over placebo in the adolescent subgroup.[115]
It is the active S-enantiomer of citalopram, with double the potency of citalopram. It has a half-life of 27 to 32 hours. Similar to citalopram, it is a weak 2D6 inhibitor with minimal drug-to-drug interactions.
Sertraline
Has been found to be more effective than placebo only when the results of two trials were pooled.[116]
It has a 26-hour half-life and is a moderate P450 enzyme inhibitor, although at high doses it is a potent inhibitor of 2D6. At high doses, drug-to-drug interactions need to be considered. Stronger evidence for efficacy in anxiety and obsessive-compulsive disorder.
Citalopram
Has only one positive trial.[117]
It has minimal effect on the P450 enzyme system, thus limited drug-to-drug interactions. Use caution at higher doses due to risk of prolongation of the QT interval.
Due to a lack of efficacy and being poorly tolerated in children, paroxetine is not recommended for use in children.[66][118][119][120]
There are no paediatric depression trials for fluvoxamine.
Adverse effects and safety of SSRIs
Overall, most of the SSRIs and non-SSRIs (considered for use in later steps) are well tolerated by children and adolescents, and adverse effects are mild and short-lived. However, potential adverse effects and precautions need to be discussed thoroughly with the child and parents, to ensure safety and improve adherence. Children and adolescents treated for depression with SSRIs (and serotonin–noradrenaline reuptake inhibitors [SNRIs]) appear to experience a greater number of adverse effects (including severe adverse effects) than those treated with placebo, indicating a need for a careful and individualised approach to prescribing that considers the relationship between anticipated clinical benefit and possible side effects.[109] The FDA issued a black box warning on suicidality associated with paediatric use of antidepressants in 2004.[110] Common adverse effects of SSRIs include:
Headaches
Nausea
Diarrhoea
Abdominal pain
Insomnia
Sedation
Tremors
Increased bleeding time.
Sexual adverse effects related to SSRIs occur frequently in adults and adolescents (up to 40% of patients), but these adverse effects are not always discussed at patient review.
Most of these effects may be mitigated by simple strategies, such as:
Initiating medication at a low dose
Titrating slowly
Taking medication with food, to avoid nausea or gastric discomfort
Taking sedating medications at bedtime and alerting medication in the morning.
Uncommon but more concerning adverse events include:
Activation
Induction of manic/hypomanic symptoms
Suicidal thoughts and behaviours.
A careful review of family history, first-degree relatives' response to medication, previous medication history, and concurrent use of other medications for potential drug-to-drug interactions may better prepare the patient, family, and clinician to avoid negative consequences. These considerations may also help the clinician make the initial medication choice.
Suicidal thoughts are part of the presentation of depression, and may occur prior to or during treatment. Although there is insufficient evidence to support suggestions that antidepressants could cause suicidal ideation and behaviour, both the FDA analysis and a re-analysis of all the controlled trials of antidepressant therapy have indicated an increased association of suicidal ideation but not suicide attempt with antidepressant treatment versus placebo. The risk is relatively small, comprising only a 1% to 2% increased risk of suicidal ideation with antidepressant use (3% to 4%) compared with placebo (2%).[121][122] Eleven times more youth who are treated with an antidepressant will respond to the medication than will develop suicidal behaviour.[121] It is recommended that children and adolescents should be monitored closely during the early weeks of initiating antidepressant treatment and during dose adjustments. Rating scales may be used to assess and monitor adverse effects and adverse events during depression treatment, such as:
Safety Monitoring Uniform Report Form[123]
Toronto Side Effects Scale[124]
Liverpool University Neuroleptic Side Effects Scale[125]
Mental Health Therapeutic Outcomes Tool.[126]
Children need to be monitored closely with a more frequent follow-up schedule when initiating a new treatment, or during dose change, as adverse effects and adverse events are more likely to occur during those periods. A minimum of 1 to 2 visits (either face to face or virtual) every 4 weeks during the initial months of antidepressant treatment is required.
Moderate or severe depression: inadequate improvement with first SSRI
If, after 8 or more weeks of treatment with an SSRI at an adequate dose (either as a monotherapy or combined with specific psychotherapy), there is no response (no change in depression severity or functioning impairment), or only partial response (less than a significant reduction of depression severity or improvement of functioning), switching to another SSRI is recommended. Choices of a second SSRI include fluoxetine, sertraline, citalopram, and escitalopram (escitalopram is for adolescents only), depending on which was used initially. If evidence-based psychotherapy was not used initially, it should be actively instituted at this point in treatment.[127]
Moderate or severe depression: management of inadequate response to second SSRI by switching to a non-SSRI (specialist care)
If there is an inadequate response after the second SSRI, then the medication can be switched to a non-SSRI, or the SSRI could be augmented. It should be noted that current evidence to support switching to a non-SSRI or augmenting does not exist for children and adolescents. As such, these agents should only be commenced by specialists who are experts in managing depression in childhood.
Before initiating this step, a careful reassessment is important to verify the diagnosis and to rule out other contributing factors, such as unrecognised or newly emergent comorbid illness (e.g., substance use disorder), inadequacy of psychosocial intervention, unresolved stress, or a new trauma.
Choices for switching include:
Venlafaxine
Mirtazapine
Bupropion.
SNRIs seem to be more beneficial than placebo for treating children and adolescents with depression, although the effect size is small. One meta-analysis found that children and adolescents treated with SNRIs reported a greater incidence of adverse effects than those treated with placebo, including serious adverse effects such as suicidality, emphasising the need for a careful and individualised harm-benefit analysis prior to considering treatment.[109]
Venlafaxine
An SNRI. To assess the efficacy of this treatment, three controlled studies have been conducted, and all were negative. However, when the data from two studies was pooled together, the adolescent subgroup showed that venlafaxine was superior compared with placebo in reducing depression.[128][129] Venlafaxine is not recommended as a first-line choice. However, the only controlled trial for treatment-resistant depression indicated that venlafaxine was effective in treating depression in adolescents who did not respond to one SSRI.[127] In the FDA assessment, compared with other antidepressants, venlafaxine did have significantly more suicide-related adverse events than placebo.[122] A retrospective cohort study of 36,842 patients aged 6 to 18 years showed no evidence that risk of suicide attempts differed for SSRI and SNRI antidepressants.[130] Extended-release formula is recommended, which still has a relatively short half-life of 10.3 hours. UK guidelines recommend that venlafaxine should not be used for the treatment of depression in children and young people.[67]
Mirtazapine
A serotonin receptor 2 (5-HT2) antagonist, with a half-life of 20 to 40 hours. The only two multicentre paediatric mirtazapine trials were negative, possibly due to the high placebo response in the two studies.[131] The drug does not inhibit any P450 enzymes. At lower dose, mirtazapine has a strong antihistamine effect, and may also cause sedation and weight gain.
Bupropion
A potent 2D6 inhibitor with a half-life of 21 hours for the sustained-release formulation. There have been no controlled trials for bupropion, although it is frequently prescribed.[110]
Moderate or severe depression: management of inadequate response to second SSRI by augmentation strategies (specialist care)
An alternative approach to switching to a non-SSRI medication is to use augmentation strategies, especially if there is a partial response to the second SSRI. Psychotherapy (e.g., CBT or IPT) or medication may be used to augment.
In adults, lithium, triiodothyronine, atypical antipsychotic medications, and bupropion have been studied most frequently, with some indications of efficacy.[132][133][134][135][136][137][138] Atypical antipsychotics and bupropion have been used more frequently in the paediatric population as augmenting agents compared with other agents. However, paediatric controlled studies have not been done. These agents should only be commenced by specialists who are experts in managing depression in childhood. The only study of paediatric treatment-resistant depression found that adolescents who had more than nine CBT sessions in addition to treatment with a second SSRI or venlafaxine were more likely to have a positive response than adolescents who received fewer CBT sessions.[139]
Bupropion is one of the more frequently used augmenting agents, although no paediatric trials have been conducted on it. Sustained-release bupropion may be used to augment.
Atypical antipsychotics have been used clinically to augment antidepressant effect. Quetiapine, aripiprazole, and ziprasidone are used more frequently in clinical settings, because risperidone and olanzapine may cause significant weight gain and metabolic effects. No controlled trials have been conducted in depressed children, although a chart review of 10 cases indicated the efficacy of adding quetiapine to treat depressed adolescents who have not responded to an adequate trial of an SSRI. For all other atypical antipsychotics except ziprasidone, weight, lipid profile, and fasting glucose need to be monitored.
Lamotrigine has been studied in the management of unipolar depression and bipolar depression, though studies are limited. In one study that included chart reviews of 42 adolescent patients with treatment-resistant depression, 22 showed improvement with lamotrigine.[140]
Lithium has been studied as an augmenting agent most frequently in adults, with more than 10 controlled trials. In most of the studies, lithium was used as an augmenting agent for tricyclic antidepressants (TCAs). Only two open paediatric trials also used lithium to augment a TCA.[141][142] Blood levels need to be monitored to avoid toxicity. Thyroid and renal function also need to be monitored regularly.
Levothyroxine has been studied, but its efficacy is inconclusive according to adult depression data. Neither controlled nor open trials have been done in the paediatric population. Thyroid-stimulating hormone levels need to be monitored to avoid negative biofeedback.
Novel alternative approaches for children with treatment-resistant depression (specialist care)
If response remains poor, despite all of the possible treatments outlined up to this phase, novel and alternative treatments may be considered. These should only be commenced by specialists who are experts in managing depression in childhood. They include:
Other antidepressants (e.g., TCAs and monoamine oxidase inhibitors [MAOIs])
Biological treatments (e.g., light therapy and electroconvulsive therapy [ECT]).
Other antidepressants, such as TCAs or MAOIs, may be used for children and adolescents who have not responded to SSRIs or non-SSRIs. TCAs have not proved to be effective in treating paediatric depression, and tend to produce more adverse events.[143]
[ ]
UK guidelines recommend that TCAs should not be used for the treatment of depression in children and young people.[67] Because of the adverse effects and the difficulty of managing diet in children and adolescents, MAOIs have not been recommended for use in paediatric depression. However, the patch form of a selective MAOI, selegiline, may bypass the concern and become an alternative treatment for young people with depression resistant to other treatment. A study comparing the selegiline patch and placebo in adolescents with major depressive disorder demonstrated safety of the active medication, although response rates were similar for both groups (58.6% vs. 59.3%).[144]
Biological treatments include light therapy and ECT. Light therapy is recommended for seasonal affective disorder (SAD), and its efficacy has been demonstrated in a few case series and one controlled study in young people with SAD.[145] A recent review and meta-analysis indicates that light therapy may be effective for non-seasonal depression in adults.[146]
Case reports on the efficacy of ECT in paediatric depression have appeared for more than 60 years.[147] However, there have not been any controlled trials conducted in the paediatric population. Series reports indicate that the best response is in youth with catatonia, psychosis, and bipolar depression. There is a negative perception regarding ECT in some countries, including in several US states, where the use of ECT in children and adolescents has been banned. This, and the fact that generally medication and psychotherapy are readily available, has led to infrequent use of ECT as a treatment modality, even in children and young people with treatment-resistant depression.
Complementary and alternative medicine treatment (CAM)
Although complementary and alternative medicine is used frequently around the world for treating paediatric depression, including in the US, there is extremely limited empirical evidence for its efficacy.[148] UK guidelines states that St. John's wort should not be prescribed for the treatment of depression in children and young people, due to insufficient evidence of efficacy and known drug interactions.[67] US guidelines have not discussed the use of natural remedies in the management of paediatric depression.
Among the natural remedies, the most frequently used and studied remedies for depression include:
St. John's wort
Omega-3 fatty acids
S-adenosyl methionine (SAMe).
St. John's wort is the most frequently used herbal remedy for depression. It is the number one antidepressant prescribed for children in Germany.[149] There are many adult-controlled studies that indicate inconsistent efficacy in treating adult depression.[150][151] No controlled studies have been conducted in children with depression. Several open-label studies indicate that St. John's wort is well tolerated by children, and that it is effective in treating depression in children.[152][153][154] However, it is not recommended to treat moderate to severe cases of depression, due to unclear efficacy. St. John’s wort has also been associated with longer coagulation time; in addition, it increases metabolism of contraceptives and can result in unwanted pregnancy. Caution is necessary with concurrent use of other medications, due to potential drug-to-drug interactions. This is a particular concern with concurrent use of other antidepressants, because of the risk of serotonergic syndrome.
Omega-3 fatty acids are suggested to be beneficial in many health problems. A combination of eicosapentaenoic acid and docosahexaenoic acid from fish oil, rather than omega-3 fatty acids from plants, is effective. Results from adult depression studies indicate benefit in reducing depression.[155] Only one small controlled study of depressed children has been done. This demonstrated that 70% of children who received 1000 mg daily dose of omega-3 fish oil, versus 0% of children who received placebo, had a reduction in their depression severity.[156] Fish oil is well tolerated in general, but high doses are not recommended due to inhibition of platelet aggregation and concern for potential bleeding. Fish oil may also interact with anticoagulants, so it is not recommended for use concurrently with those drugs. There is a concern about contamination of fish oil from heavy metals and pesticides. Algae omega-3 may be a purer alternative source of omega-3 fatty acids compared with fish oil.
SAMe is important in the synthesis of neurotransmitters, such as serotonin, noradrenaline (norepinephrine), and dopamine. Adult depression trials of SAMe indicated superior efficacy to placebo and comparable efficacy to TCAs.[157] SAMe may also be effective as an augmenting agent.[158] No paediatric depression studies are available, except for case reports that indicate efficacy in treating depression in children and adolescents.[159] Interactions of SAMe with other medications appear to be infrequent.[151]
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