Depression

Essentials of Diagnosis

• In most depressions

  • Mood varies from mild sadness to intense guilt, worthlessness, and hopelessness

  • Difficulty in thinking and concentration, with rumination and indecision

  • Loss of interest, with diminished involvement in activities

  • Somatic complaints

  • Disrupted, reduced, or excessive sleep

  • Loss of energy, appetite, and sex drive

• In some severe depressions

  • Psychomotor disturbance: retardation or agitation

  • Delusions of a somatic or persecutory nature

  • Withdrawal from activities

  • Suicidal ideation

General Considerations

• Sadness and grief are normal responses to loss; depression is not

• Unlike grief, depression is marked by a disturbance of self-esteem, with a sense of guilt and worthlessness

• Persistent depressive disorder (dysthymia) is a chronic depressive disturbance with symptoms generally milder than in a major depressive episode

Demographics

• Up to 30% of primary care patients have depressive symptoms

Symptoms and Signs

• Anhedonia

• Withdrawal from activities

• Feelings of guilt

• Poor concentration and cognitive dysfunction

• Anxiety

• Chronic fatigue and somatic complaints

• Diurnal variation with improvement as the day progresses

• Vegetative signs

  • Insomnia

  • Anorexia

  • Constipation

• Occasionally, severe agitation and psychotic ideation

• Atypical features

  • Hypersomnia

  • Overeating

  • Lethargy

  • Mood reactivity

Differential Diagnosis

• Bipolar disorder or cyclothymia

• Adjustment disorder with depressed mood

• Dysthymia

• Premenstrual dysphoric disorder

• Major depression with postpartum onset: usually 2 weeks to 6 months postpartum

• Seasonal affective disorder

  • Carbohydrate craving

  • Lethargy

  • Hyperphagia

  • Hypersomnia

Laboratory Tests

• Complete blood count

• Serum thyroid-stimulating hormone

• Serum folate

• Toxicology screen may be indicated

• Blood tests to diagnose depression and predict antidepressant response are being developed

Medications

• See Table 25–7 and Figure 25–2

• Selective serotonin reuptake inhibitors (SSRIs) and atypical antidepressants

  • Generally lack anticholinergic or cardiovascular side effects

  • Most are activating and should be given in the morning

  • Some patients may experience sedation with paroxetine, fluvoxamine, and mirtazapine

  • Clinical response varies from 2 to 6 weeks

  • Common side effects are headache, nausea, tinnitus, insomnia, nervousness

  • Sexual side effects (eg, erectile dysfunction) are very common and may respond to sildenafil

  • "Serotonin syndrome" may occur when SSRIs are taken in conjunction with monoamine oxidase inhibitors or selegiline

  • With the exception of paroxetine, SSRIs should be tapered over weeks to months to avoid a withdrawal syndrome

  • Most studies show that SSRIs are not associated with birth defects

  • Paroxetine has some association with a fetal heart defect, thus should be avoided in favor of other SSRIs during pregnancy

  • Vortioxetine

    • Blocks serotonin reuptake, is a partial agonist of the 5-HT_1A receptor, and affects a variety of other serotonin receptor sites

    • Has demonstrated efficacy in improving cognitive symptoms of depression and has received regulatory approval for this indication in Europe

    • Typical dose: 10 mg/day orally and may be increased to 20 mg/day

    • Side effects attributed to its serotonergic effects include gastrointestinal upset and sexual dysfunction

• Tricyclic antidepressants (TCAs)

  • Mainstay of treatment before SSRIs

  • Start at low dose and increase by 25 mg weekly to avoid sedation and anticholinergic side effects

  • Overdose can be serious

• Monoamine oxidase inhibitors (MAOIs)

  • Commonly cause orthostatic hypotension and sympathomimetic effects

  • Third-line agents due to dietary restrictions and drug–drug interactions

  • However, with the availability of selegilene, which is a skin patch, the dietary restrictions are not necessary in the lowest dosage strength (6 mg/24h)

• Potential for withdrawal syndromes requires gradual tapering of antidepressants

• Drug selection should be influenced by any history of prior responses

• If response is inadequate, either switch to a second agent or try augmenting the first agent with

  • Bupropion (150–450 mg/day), lithium (eg, 300–900 mg/day orally), or thyroid medication (eg, liothyronine, 25–50 mcg/day orally) or

  • A second-generation antipsychotic, such as aripiprazole (5–15 mg/day)

• Stimulants such as dextroamphetamine (5–30 mg/day) and methylphenidate (10–45 mg/day) can be used for short-term treatment of medically ill and geriatric patients or in refractory cases

• Ketamine infusion

  • Has been shown to lead to a rapid improvement in depressive symptoms in 50–70% of patients

  • However, effects of a single treatment are short lived

• Esketamine

  • The nasal spray formulation is FDA-approved for the treatment of depression when inadequately treated by two other antidepressant medications

  • However, there are ongoing concerns about long-term use of esketamine or ketamine, including the risk of abuse and longer-term impacts on mood and suicidality

• Allopregnanolone

  • A neurosteroid an allosteric modulator of GABA-a receptors

  • Approved for the treatment of postpartum depression

  • Like ketamine, allopregnanolone is administered intravenously and the antidepressant effects are rapid

  • Most common side effects

    • Headache

    • Dizziness

    • Somnolence

Therapeutic Procedures

• Electroconvulsive therapy (ECT)

  • Most effective (45–85% remission rate) treatment for severe depression with contraindications to medications or for depression refractory to medications

  • Remission rates in treatment-resistant depression are lower (around 48%)

  • Most common side effects are headache and memory disturbances, which are usually short-lived

• Transcranial magnetic stimulation (TMS)

  • Appears to be effective in nonpsychotic depression

  • Involves the application of electromagnetic pulses to the dorslolateral prefrontal cortex

  • Approved by the FDA for individuals who have not tolerated or responded to standard medications

  • Usually delivered in a course of 20–30 sessions over 4–6 weeks

  • While not as effective as ECT, TMS neither requires general anesthesia nor produces cognitive side effects

• Vagus nerve stimulation is approved for treatment of extremely refractory depression, though there is limited clinical experience

• Deep brain stimulation continues to be explored for the treatment of refractory depression but controlled studies have not shown success

• Psychological

  • Medication and psychotherapy are more effective than either modality alone

  • Psychotherapy is seldom possible in the acute phase of severe depression

• Social

  • In depressions involving alcohol abuse, early involvement in recovery programs is important to therapeutic success

  • Family, employers, and friends can help mobilize a recently depressed patient

Follow-Up

• Medication trials should be monitored every 1–2 weeks until 6 weeks, when the effectiveness of the medication can be assessed

• If successful, medications should be continued for 6–12 months before tapering is considered

• Medications should be continued indefinitely in patients with their first episode before age 20, more than two episodes after age 40, or a single episode after age 50

• Tapering of medications should occur gradually over several months

Complications

• Suicide

  • In individuals hospitalized for depression, the lifetime risk rises to 4–6%

  • There is an association between antidepressant use and increased suicidality in patients under 25 years of age (monitor closely during the first 6–8 weeks of treatment)

  • There are four major groups who attempt suicide

    • Those who are overwhelmed by problems in living

    • Those who are clearly attempting to control others

    • Those with severe depressions

    • Those with psychotic illness

Prevention

• Patients at risk for suicide should receive medications in small quantities

• Guns and drugs should be removed from the patient's house

• High-risk patients should be asked not to drive

Prognosis

• Patients frequently respond well to a full trial of drug treatment

When to Refer

• When depression is refractory to antidepressant therapy

• When depression is moderate to severe

• When suicidality or significant loss of function is present

• With active psychosis or history of mania

When to Admit

• Patients at risk for suicide

• Complex treatment modalities are required