eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics
Depression: Treatment & Medication
Updated: Jul 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Opinions vary about whether cognitive-behavioral psychotherapy, pharmacotherapy, or a combination of both should be offered as first-line treatment for children and adolescents with MDD. Safety is always the first concern in the evaluation of MDD in children and adolescents. Cognitive-behavioral therapy has been shown in multiple randomized clinical trials to be effective in the treatment of mild-to-moderate MDDs in children and adolescents. Evidence from randomized clinical trials suggests efficacy in the treatment of moderate-to-severe MDD using 3 selective serotonin reuptake inhibitors (SSRIs): fluoxetine, sertraline, and citalopram.
Overall, the choice of the initial acute therapy depends on the severity, number of prior episodes, chronicity, subtype, age of the patient, contextual issues (eg, family conflict, academic problems, exposure to negative life events), compliance with treatment, previous response to treatment, and the motivation of the patient and family for treatment. In mild cases, psychosocial interventions are often recommended as first-line treatments, whereas, in the most severe cases, medication in addition to psychotherapeutic intervention is often recommended.
Treatment of a child or adolescent who is depressed should occur within a biopsychosocial context. Such an approach includes the psychotherapies (eg, individual, family, group), medication management, social skills training, and educational assessment and planning. The clinician should choose a treatment setting prior to initiation of a treatment plan. The clinician must carefully assess the risk for suicide in any child who is depressed. If a child is obsessed with thoughts of suicide or has definite plans, the patient must be hospitalized. Also, the clinician should weigh factors, such as the child's ability to function and the stability of the family plus any history of previous suicide attempts, when determining whether or not to hospitalize a child or adolescent.
Psychotherapy appears to be a useful initial acute treatment for mild-to-moderate depression. Cognitive-behavioral therapy has been extensively studied, and other forms of psychotherapy, such as psychodynamic psychotherapy, interpersonal psychotherapy, and family therapy, have been found to be effective and are used clinically. More studies that compare the complementary and differential effects of these therapies are needed.
Antidepressant medications may be indicated for children and adolescents with nonrapid cycling bipolar depression, psychotic depression, depression with severe symptoms that prevent effective psychotherapy, and depression that does not respond to psychotherapy; however, given the psychosocial context in which depression occurs, pharmacotherapy is insufficient as the only treatment. Even when the patient's mood has been stabilized using a medication-only treatment, evidence suggests that the environmental and social problems associated with MDD remain, preventing the necessary full stabilization.
Combined treatment increases the likelihood not only of mitigating depressive symptomatology but also increases the likelihood of increasing self-esteem, coping skills, and adaptive strategies and improving family and peer relationships. Psychodynamic psychotherapy, interpersonal therapy, cognitive-behavioral therapy, behavior therapy, family therapy, supportive psychotherapy, and group psychotherapy have all been used for the treatment of youths with MDD.
Many clinicians have found psychodynamic psychotherapy useful in the treatment of depression in youths. Controlled studies using psychodynamic psychotherapy for the treatment of depression in children and adolescents are particularly difficult to design and expensive to conduct but are greatly needed. Psychodynamic psychotherapy can help youths understand themselves, identify feelings, improve self-esteem, change maladaptive patterns of behavior, interact more effectively with others, and cope with ongoing and past conflicts.
Interpersonal therapy focuses on problem areas of grief, interpersonal roles, disputes, role transitions, and interpersonal difficulties. In a 1996 study, Mufson and Fairbanks found that interpersonal therapy may be useful in the acute treatment of adolescents with MDD.18 They also found the rate of relapse to be relatively low after acute interpersonal therapy treatment.
Cognitive-behavioral therapy is one of the most frequently studied psychotherapy treatments. Its use in treating MDD is based on the premise that patients who are depressed have a distorted view of themselves, the world, and the future. These cognitive distortions contribute to their depression and can be identified and counteracted with cognitive-behavioral therapy. In nonclinical samples, 4 studies have shown group cognitive-behavioral therapy to be better than no intervention for children and adolescents in the reduction of depressive symptomatology and improvement of self-esteem.
In most clinical samples, cognitive-behavioral therapy was found to be superior to other manualized treatments, including relaxation training and family and supportive therapy; however, all clinical studies of cognitive-behavioral therapy found a high rate of relapse on follow-up, suggesting the need for continuation treatment. Given the high rate of relapse and recurrence of depression, continuation therapy is recommended for all patients for at least 6-12 months.
During the continuation phase, observe patients at least monthly, depending on clinical status, functioning, support systems, environmental stressors, motivation for treatment, and the presence of comorbid psychiatric or other medical disorders. In this phase, psychotherapy can be used not only to consolidate the skills learned during the acute phase and help patients cope with the psychosocial sequelae of the depression but also to address the antecedents, contextual factors, environmental stressors, and intrapsychic conflicts that may contribute to a relapse. If the patient is taking antidepressants, psychotherapy can be used to foster medication compliance. The only continuation study in depressed youths suggests that monthly cognitive-behavioral therapy sessions may be effective to prevent relapses of depression in adolescents.19
Several factors appear to be related to the response to psychotherapy, including age at onset of depression, severity of depression, presence of comorbid psychiatric disorders (eg, anxiety, dysthymia, substance abuse), lack of support, parental psychopathology, family conflict, exposure to stressful life events, socioeconomic status, quality of treatment, therapist's expertise, and motivation of both patient and therapist. A combination of the particular elements of cognitive-behavioral therapy, interpersonal therapy, psychodynamic psychotherapy, and other psychotherapies may be brought together in the best interests of the patient. In 1997, Brent et al reported that individual supportive treatment was found to be considerably less efficacious than cognitive-behavioral therapy in adolescents who were depressed.20
Adolescents whose parents suffer from depression are at increased risk of developing depressive disorders. Garber et al (2009) studied 316 adolescents whose parents were diagnosed with current or prior depressive disorders. The adolescents had a past history of depression, current elevated but subdiagnostic depressive symptoms, or both. The objective was to determine if the effects of a group cognitive behavioral prevention program prevented depression onset compared with usual care. Rate and hazard ratio were lower among adolescents participating in a cognitive behavioral program than in those who underwent usual care. Adolescents participating in a cognitive behavioral program also self-reported greater improvement in depressive symptoms than those who underwent usual care. These effects were not observed in adolescents with a currently depressed parent, and, in these adolescents, the cognitive behavioral program was not shown to be more effective than usual care in preventing depression.21
Medication
Studies on the use of medications for youths with MDD are few, and some have methodologic problems. Additionally, very few pharmacokinetics studies have been performed in children. The few studies in children have focused on the effects of tricyclic antidepressants (TCAs), with few studies addressing SSRIs. Other antidepressants, including heterocyclics (eg, amoxapine, maprotiline), monoamine oxidase inhibitors (MAOIs), bupropion, venlafaxine, and nefazodone, have been found to be effective in the treatment of adults who are depressed.
The clinician needs to inform parents and patients about adverse effects, the dose, the timing of therapeutic effect, and the danger of overdose, particularly with TCAs, before initiating pharmacologic treatment. Parents should take responsibility for medication storage and administration, especially with younger children and children at risk for suicide. Because of the potential of the TCAs to induce a fatal overdose, the clinician must carefully determine the exact amount of medication to be prescribed at each appointment.
The TCAs require a baseline ECG, resting blood pressure, and pulse. Weight should also be frequently documented. No laboratory tests are currently indicated before or during the administration of the SSRIs. No other tests are indicated in a healthy child before starting antidepressants.
Because of reports that SSRIs are effective for the treatment of youths with MDD and because of reports that SSRIs have a relatively safe adverse effect profile, very low lethality after overdose, and only once daily administration, the clinician may support the use of the SSRIs as first-line medications.
Open studies, such as those in 1997 by Leonard et al22 and Rey-Sanchez and Gutierrez-Casares,23 have reported 70-90% response to the SSRIs in the treatment of adolescents with MDD. Also in 1997, Emslie et al conducted an 8-week double-blind study of the treatment of a large sample of youths with MDD and showed that children and adolescents responded significantly better to fluoxetine than to placebo (58% vs 32%).24 Despite the significant response to fluoxetine, many patients had only partial improvement; only 31% achieved full remission.
A possible explanation for the partial response is that the effective treatment may involve variation in dose or length of treatment. Also, the ideal treatment likely involves a combination of pharmacologic and psychosocial interventions. Except for lower initial doses, the administration of SSRIs in children and adolescents is similar to the treatment protocols used for adult patients. The clinician should treat patients with adequate and tolerable doses for at least 4 weeks. At 4 weeks, if the patient has not shown even minimal improvement, the clinician should consider increasing the dose. If, at this time, the patient shows improvement, the dose can be continued for at least 6 weeks. On the contrary, if no improvement is apparent at 6 weeks, other treatment strategies should be considered.
The clinician must cautiously apply this recommendation; whether longer trials with SSRIs increase the number of patients with late improvement is not clear. The SSRIs possess a relatively flat dose-response curve, suggesting that maximal clinical response may be achieved at minimum effective doses; therefore, adequate time must be allowed for clinical response and frequent early dose adjustments must be avoided. Blood levels are rarely indicated in clinical settings, but they may help clarify concerns about toxicity or medical compliance.
The adverse effects of all SSRIs in children are similar to those in adults. They are dose-dependent and may subside with time. SSRIs may induce mania, hypomania, and behavioral activation, in which patients become impulsive, silly, agitated, and daring. Other adverse effects include GI symptoms, restlessness, diaphoresis, headaches, akathisia, bruising, and changes in appetite, sleep, and sexual functioning. The long-term adverse effects of SSRIs are not yet known.
A small number of case reports, such as those by King et al in 199425 and Teicher et al in 1993,26 have described a putative association between SSRI administration and increased suicidality (perhaps linked to behavioral activation or akathisia). However, although such phenomena may have occurred in a small number of cases, several studies suggest that SSRIs, like other antidepressants, generally reduce the risk of suicide in adult patients who are depressed.
SSRIs are greatly preferred over the other classes of antidepressants. Because the adverse effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.
Physicians are advised to be aware of the following information and use appropriate caution when considering treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and, thus, could not be definitively linked to drug treatment.
In September 2004, the results of an FDA analysis suggested that the risk of emergent suicidality in children and adolescents taking SSRIs was real. The FDA advisors (Columbia University) recommended the following:
- A "black-box" warning label be placed on all antidepressants, indicating that they increase the risk of suicidal thinking and behavior (suicidality)
- A patient information sheet (Medication Guide) be provided to the patient and their caregiver with every prescription
- The results of controlled pediatric trials of depression be included in the labeling for antidepressant drugs
The committees recommended that the products not be contraindicated in the United States because access was important for those who could benefit from them. For more information, see the FDA Statement on Recommendations of the Psychopharmacologic Drugs and Pediatric Advisory Committees.
This remains a controversial issue. Some studies have argued that a decline in youth suicide rates coincided, to a striking extent, with significant increases in the prescription of antidepressants (mostly SSRIs) to adolescents.27,28,29 The Treatment for Adolescents with Depression Study (TADS) also lends support for fluoxetine's efficacy in adolescent depression, notably the combined use of fluoxetine with cognitive-behavioral therapy.30 Data from the TADS study also suggested a possible protective effect of cognitive behavioral therapy against suicidality when used in combination with fluoxetine.
Additionally, a study of more than 65,000 children and adults treated for depression between 1992 and 2003 by the Group Health Cooperative in Seattle found that suicide risk declines, not rises, with the use of antidepressants.31 This is the largest study to date to address this issue.
Currently, evidence does not suggest that obsessive-compulsive disorder (OCD) and other anxiety disorders treated with SSRIs are associated with an increased risk of suicide.
Abrupt discontinuation of SSRIs with shorter half-lives, such as paroxetine, may induce withdrawal symptoms, some of which may mimic a relapse or recurrence of a depressive episode (eg, tiredness, irritability, severe somatic symptoms). The withdrawal symptoms can appear after as few as 6-8 weeks of SSRI treatment. For clinical practice and education, the FDA has recommended that physicians who prescribe these medications should closely monitor patients with observation that "would generally include at least weekly face-to-face contact during the first 4 weeks of treatment" with specific visit intervals specified after those 4 weeks.32
Awareness of possible interactions with other medications is important. To varying degrees, the SSRIs inhibit the metabolism of several medications that are metabolized by the diverse clusters of hepatic cytochrome P450 isoenzymes (eg, TCAs, neuroleptics, antiarrhythmics, benzodiazepines, carbamazepine, theophylline, warfarin, terfenadine [removed from United States market]). In addition, interactions of SSRIs with other serotonergic medications, particularly MAOIs, may induce the serotonergic syndrome, marked by agitation, confusion, and hyperthermia. SSRIs also have a high rate of protein binding, which can lead to increased therapeutic or toxic effects of other protein-bound medications. MAOIs should not be administered less than 5 weeks after discontinuation of fluoxetine and less than 2 weeks for other SSRIs. Also, the clinician should not prescribe SSRIs within 2 weeks after stopping the MAOIs.
Although open studies using TCAs suggest their usefulness in treating youths with MDD, several randomized controlled studies have shown 50-60% response to both TCAs (nortriptyline, desipramine, amitriptyline) and placebo. Consider these results with caution because of methodologic limitations, including small sample sizes, short-duration trials, and inclusion of patients with mild depression and comorbid disorders that may have had good responses to placebo.
TCAs are no longer considered the first-line treatment for youths with depressive disorders; however, individual cases may respond better to TCAs than to other medications. TCAs may also be useful for youths with comorbid ADHD, enuresis, and narcolepsy, as well as for augmentation strategies. When using TCAs, the clinician should monitor plasma levels to measure compliance and to avoid toxicity.
Selective serotonin reuptake inhibitor (SSRI) antidepressants
These are a relatively new group of medicines used to treat emotional and behavior problems, including depression, panic disorder, obsessive-compulsive disorder, bulimia, and posttraumatic stress disorder in adults. These medications are beginning to be used to treat the same problems in children and adolescents. Serotonin is a chemical that exists naturally in the brain. The SSRIs increase brain serotonin to reference range levels. SSRIs include, but are not limited to, the following medications: fluoxetine, paroxetine, sertraline, citalopram, and fluvoxamine.
Fluoxetine (Prozac)
Antidepressant agents chemically unrelated to the tricyclic, tetracyclic, or other available antidepressants. Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine.
Adult
20-80 mg PO qd
Pediatric
5 mg/d PO initially, may increase qwk; not to exceed 20 mg/d
Potent inhibitor of CYP450 isoenzymes 1A2, 2C9, 2C19, 2D6, and 3A4; may decrease clearance of isoenzyme substrates (eg, TCAs, cisapride, theophylline, imipramine); increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAOIs and highly protein-bound drugs; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2 wk before SSRIs
Documented hypersensitivity; concurrent MAOI use or use within 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Increased physician contact and monitoring is required when using SSRIs with youths who have seizure disorder, hepatic or renal disease, or diabetes; a gradual withdrawal of at least 1 wk is preferred when discontinuing use of SSRIs; possible serious adverse effects that require physician attention are rash or hives, seizures, and heatstroke; other possible adverse effects include nausea, diarrhea, headache, anxiety, insomnia, restlessness, dry mouth, sleepiness, tremor, excessive sweating, apathy, decreased sexual interest, weight loss, weight gain, and hypomania
Paroxetine (Paxil)
Potent selective inhibitor of neuronal serotonin reuptake. Has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance therapy, make dosage adjustments to maintain patient on lowest effective dosage and reassess patient periodically to determine need for continued treatment.
Adult
10-50 mg PO qd
Pediatric
<18 years: Not established; studies have used 10 mg/d PO initially, may increase qwk; not to exceed 60 mg/d
CYP3A4 inhibitor; may decrease clearance of CYP3A4 substrates (eg, thioridazine, cisapride, TCAs theophylline); phenobarbital and phenytoin decrease effects of paroxetine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of paroxetine
Documented hypersensitivity; concurrent administration with MAOIs or administration within 14 d of discontinuing MAOIs
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Newborn infants exposed to SSRIs during the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; preliminary analysis of a retrospective study shows increased congential malformations as a whole, particularly for cardiovascular malformations, with paroxetine compared to other antidepressants with exposure during the first trimester
Increased physician contact and monitoring is required when using SSRIs with youths who have seizure disorder, hepatic or renal disease, or diabetes; a gradual withdrawal of at least 1 wk is preferred when discontinuing use of SSRIs; possible serious adverse effects that require physician attention are rash or hives, seizures, and heatstroke; other possible adverse effects include nausea, diarrhea, headache, anxiety, insomnia, restlessness, dry mouth, sleepiness, tremor, excessive sweating, apathy, decreased sexual interest, weight loss, weight gain, and hypomania
Sertraline (Zoloft)
Selectively inhibits presynaptic serotonin reuptake.
Adult
50-200 mg PO qd
Pediatric
25 mg/d PO initially, may increase qwk; not to exceed 200 mg/d in divided doses
Inhibits CYP450 isoenzymes 2C9, 2C19, and 3A4, may decrease clearance of isoenzyme substrates (eg, TCAs, cisapride, buspirone, sumatriptan); increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin
Documented hypersensitivity; current administration of MAOIs or administration in previous 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Increased physician contact and monitoring is required when using SSRIs with youths who have seizure disorder, hepatic or renal disease, or diabetes; a gradual withdrawal of at least 1 wk is preferred when discontinuing use of SSRIs; possible serious adverse effects that require physician attention include rash or hives, seizures, and heatstroke; other possible adverse effects include nausea, diarrhea, headache, anxiety, insomnia, restlessness, dry mouth, sleepiness, tremor, excessive sweating, apathy, decreased sexual interest, weight loss, weight gain, and hypomania; caution with preexisting seizure disorders, recent myocardial infarction, unstable heart disease, and hepatic or renal impairment; decreased sexual interest is observed more commonly by report than with other SSRIs
Fluvoxamine
Potent selective inhibitor of neuronal serotonin reuptake. Does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and, thus, has fewer adverse effects than tricyclic antidepressants.
Adult
50-300 mg PO qd
Pediatric
25 mg/d PO initially, may increase qwk; not to exceed 200 mg/d
Risk of a hypertensive crisis increases with coadministration with MAOIs; inhibits CYP450 isoenzymes 1A2, 2C9, 2C19, 2D6, and 3A4; fluvoxamine potentiates effect of triazolam and alprazolam, reduce dose by at least 50% with concurrent administration; reduce the dose of theophylline by one third and monitor plasma levels if taking it concurrently with fluvoxamine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of fluvoxamine
Documented hypersensitivity; current administration of MAOIs or administration in the previous 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Increased physician contact and monitoring is required when using SSRIs with youths who have seizure disorder, hepatic or renal disease, or diabetes; a gradual withdrawal of at least 1 wk is preferred when discontinuing use of SSRIs; possible serious adverse effects that require physician attention are rash or hives, seizures, and heatstroke; other possible adverse effects include nausea, diarrhea, headache, anxiety, insomnia, restlessness, dry mouth, sleepiness, tremor, excessive sweating, apathy, decreased sexual interest, weight loss, weight gain, and hypomania
Tricyclic antidepressants
From the 1960s to the late 1980s, TCAs represented the primary pharmacologic treatment for depression in the United States. Therapeutic effects of TCAs are thought to be caused by their ability to block the reuptake of the neurotransmitters serotonin and norepinephrine in nerve terminals, which results in alterations in the sensitivity of various neuroreceptors.
TCAs should be initiated at low doses to minimize adverse effects; in adolescents, TCAs are usually prescribed in once-a-day bedtime doses. Because children metabolize medications more quickly than adults, prepubertal children usually require bid dosing.
Imipramine (Tofranil)
Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. Use parenteral administration for starting therapy only in patients unable or unwilling to use PO medication.
Adult
Required dosage for depression varies among patients and should be individualized
25-75 mg/d PO initially, may titrate upwards; not to exceed 300 mg/d
Pediatric
Children: 1.5 mg/kg/d PO initially, may increase by increments of 1 mg/kg/d q3-4d; not to exceed 5 mg/kg/d qd or divided bid/qid
Adolescents: 25-50 mg/d PO initially, increase dose gradually; not to exceed 200 mg/d in single or divided doses
Increases toxicity of sympathomimetic agents (eg, isoproterenol, epinephrine) by potentiating effects; inhibits antihypertensive effects of clonidine
Documented hypersensitivity; narrow-angle glaucoma; acute recovery phase following myocardial infarction; concurrent administration of MAOIs or fluoxetine or administration in the previous 2 wk (avoid)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Can cause tachycardia; perform ECG before administration; may repeat ECG as dose is increased; because tricyclic medications can increase risk of seizures, the value of an EEG should be considered before initiation of medication; adverse effects include dry mouth, constipation, dizziness, weight gain, loss of appetite and weight loss, sleepiness, irritability, sun sensitivity, nightmares, decreased sexual interest, hypertension, hypotension, nausea, urinary retention, blurred vision, mania, and hypomania
Nortriptyline (Pamelor, Aventyl)
Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS.
Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.
Adult
Required dosage for depression varies among patients and should be individualized
10-50 mg/d PO initially, titrate upwards; doses >100-150 mg/d are seldom required
Pediatric
Children 6-12 years: 1-3 mg/kg/d PO or 10-20 mg/d PO divided tid/qid
Adolescents: 1-3 mg/kg/d PO or 30-50 mg/d PO divided tid/qid; not to exceed 150 mg/d
Cimetidine may increase nortriptyline levels when used concurrently; nortriptyline may increase prothrombin time in patients stabilized with warfarin
Documented hypersensitivity; narrow-angle glaucoma; administration to patients who have taken MAOIs in past 14 d
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Can cause tachycardia; perform ECG before administration; may repeat ECG as dose is increased; because tricyclic medications can increase risk of seizures, the value of an EEG should be considered before initiation of medication; adverse effects include dry mouth, constipation, dizziness, weight gain, loss of appetite and weight loss, sleepiness, irritability, sun sensitivity, nightmares, decreased sexual interest, hypertension, hypotension, nausea, urinary retention, blurred vision, mania, and hypomania
Desipramine (Norpramin, Pertofrane)
May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation or serotonin receptors.
Has been associated with sudden death and should be used with extreme caution and only after safer antidepressants have been tried with adequate doses and treatment duration.
Adult
Required dosage for depression varies among patients and should be individualized
25-75 mg/d PO initially, may gradually increase to 300 mg/d for patients with serious illness
Pediatric
Children 6-12 years: 1-3 mg/kg/d PO in divided doses
Adolescents: 25-50 mg/d PO initially; gradually increase to 100 mg/d in single or divided doses; not to exceed 2-5 mg/kg/d
Decreases antihypertensive effects of clonidine; increases effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin; carbamazepine and barbiturates decrease effects
Documented hypersensitivity; narrow-angle glaucoma; recent postmyocardial infarction; current administration of MAOIs or fluoxetine administration of them in the previous 2 wk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Sudden death has been associated with desipramine, do not use unless other safer antidepressants have been tried with adequate doses and treatment duration; can cause tachycardia; perform ECG before administration; may repeat ECG as dose is increased; because tricyclic medications can increase risk of seizures, the value of an EEG should be considered before initiation of medication; adverse effects include dry mouth, constipation, dizziness, weight gain, loss of appetite and weight loss, sleepiness, irritability, sun sensitivity, nightmares, decreased sexual interest, hypertension, hypotension, nausea, urinary retention, blurred vision, mania, and hypomania
Amitriptyline (Elavil)
Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS.
Adult
Required dosage for depression varies among patients and should be individualized
20-50 mg/d PO initially, may gradually increase to 300 mg/d
Pediatric
Dose ranges from 2-5 mg/kg/d PO
Children: Up to 3 mg/kg/d typically recommended
Adolescents: 25-50 mg/d PO initially; increase gradually to 100 mg/d in divided doses; not to exceed 200 mg/d
Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram; caffeine may worsen cardiac adverse effects
Documented hypersensitivity; administration of MAOIs in past 14 d; history of seizures; cardiac arrhythmias; glaucoma; urinary retention
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Can cause tachycardia; perform ECG before administration; may repeat ECG as dose is increased; because tricyclic medications can increase risk of seizures, the value of an EEG should be considered before initiation of medication; adverse effects include dry mouth, constipation, dizziness, weight gain, loss of appetite and weight loss, sleepiness, irritability, sun sensitivity, nightmares, decreased sexual interest, hypertension, hypotension, nausea, urinary retention, blurred vision, mania, and hypomania
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Further Reading
Keywords
major depressive disorder, MDD, manic-depressive disorder, bipolar disorder, suicide, suicidal ideation, childhood depression, serotonin, auditory hallucinations, depressed mood, sleep disturbance, catalepsy, seasonal mood disorder, seasonal affective disorder, attention deficit hyperactivity disorder, ADHD, anxiety, posttraumatic stress disorder
