Antidepressant Selcetion
- Biopsychosocial and Lifestyle Approach: Management of depression should consider biopsychosocial and lifestyle factors.
- Non-Drug Therapy: Many patients in primary care do not require drug therapy.
- Effective Treatments: Evidence-based treatments, including psychological therapies and antidepressants, are effective.
- Education on Depression: All patients should receive education about depression.
- Shared Decision Making: Critical when prescribing antidepressants, considering efficacy, tolerability, depressive presentation, patient preference, and drug interactions.
Introduction
- Major Depression Conceptualization: Best understood using a biopsychosocial and lifestyle model.
- Lifestyle Factors: Alcohol or substance misuse, lack of exercise, and poor sleep habits need addressing.
- Psychosocial Factors: Unemployment and interpersonal stress should be considered in management.
- Psychoeducation: Discuss symptoms, contributing factors, and management options with patients, and involve close contacts if appropriate.
Lifestyle Factors and Interventions for Depression
| Potential lifestyle risk factors | Interventions |
| Poor sleep pattern | Encourage good sleep hygiene – regular bedtime and wake up time, bed is for sleep and not for other activities (TV, social media). There are useful apps that provide basic psychoeducation and a sleep diary. |
| Alcohol misuse | Encourage safe drinking. If there is heavy use and the patient is seeking treatment, refer to an addiction medicine service. If they are not seeking treatment, do a brief intervention. |
| Substance misuse | Provide psychoeducation about the harmful effects of substances, advise abstinence, formal counselling or refer to addiction medicine services. |
| Smoking | Encourage smoking cessation, and consider motivational interviewing and nicotine replacement therapy. |
| Unhealthy diet | Psychoeducation about healthy diet and the harms associated with processed food. Encourage Mediterranean diet and increased intake of fruit and vegetables. |
| Lack of exercise | Encourage regular exercise (e.g. daily walks), emphasising a graded approach to exercise. |
Specific Treatments
- Psychological Treatment: Cognitive behavioral therapy is as effective as drug therapy for mild-moderate depression.
- Antidepressant Drugs: Prescribed for major depression, melancholia, psychotic depression, and when psychological therapies are ineffective or inaccessible.
Indications for Drug Therapy
- Major Depression: Marked symptoms and functional impairment.
- Melancholia: Significant psychomotor symptoms.
- Psychotic Depression: Depression with delusions or hallucinations.
- Previous Good Response: Patients who responded well to antidepressants before.
- Ineffective Psychological Therapies: When psychological therapies are inaccessible or ineffective.
Drug Selection
- Considerations:
- Efficacy
- tolerability
- type of depression
- safety– risk of overdose, interactions with other drugs or medical disorders (some groups need special consideration, such as older patients and women during pregnancy and lactation, as the baby will be exposed to the antidepressant)
- patient preference.
- Pharmacogenetic Data: Not essential for routine antidepressant choice; genetic testing not usually necessary.
Balancing Efficacy with Tolerability
- Network Meta-Analysis: Confirms antidepressant efficacy; dual-acting drugs (SNRIs, tricyclics) more efficacious than single-action drugs (SSRIs).
- Acceptability: Based on drop-out rates and adverse effects in clinical trials.
Efficacy of antidepressants compared to placebo
| Antidepressant | Odds ratio | 95% confidence interval |
| Amitriptyline | 2.13 | 1.89–2.41 |
| Mirtazapine | 1.89 | 1.64–2.20 |
| Duloxetine | 1.85 | 1.66–2.07 |
| Venlafaxine | 1.78 | 1.61–1.96 |
| Paroxetine | 1.75 | 1.61–1.90 |
| Fluvoxamine | 1.69 | 1.41–2.02 |
| Escitalopram | 1.68 | 1.50–1.87 |
| Sertraline | 1.67 | 1.49–1.87 |
| Vortioxetine | 1.66 | 1.45–1.92 |
| Agomelatine | 1.65 | 1.44–1.88 |
| Fluoxetine | 1.52 | 1.40–1.66 |
| Citalopram | 1.52 | 1.33–1.74 |
| Clomipramine | 1.49 | 1.21–1.85 |
| Desvenlafaxine | 1.49 | 1.24–1.79 |
| Reboxetine | 1.37 | 1.16–1.63 |
from: Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis – Andrea Cipriani, Toshi A Furukawa – www.thelancet.com Vol 391 April 7, 2018
Forest plots of network meta-analysis of all trials for efficacy (A) and acceptability (B)
Antidepressant adverse effects and their limitations on use
| Class | Major adverse effects | Ease of switching (half-life) | |||
| Weight gain | CNS effects – sedation/agitation | Sexual | Withdrawal syndrome | ||
| Selective serotonin reuptake inhibitors (SSRIs) | • | •• | ••• | ••† | •• |
| Serotonin noradrenaline reuptake inhibitors (SNRIs) | • | •• | ••• | ••• | •• |
| Serotonin modulator (vortioxetine) | • | • | •• | •• | ••• |
| Noradrenaline reuptake inhibitor (reboxetine) | • | • | •• | • | •• |
| Tricyclic antidepressants (TCAs) | ••• | ••• | ••• | ••• | ••• |
| Reversible inhibitor of monoamine oxidase A (moclobemide) | • | •• | • | • | ••• |
| Tetracyclic (mianserin) | •• | •• | • | •• | • |
| Noradrenergic and specific serotonergic (mirtazapine) | ••• | ••• | •• | •• | • |
| Monoamine oxidase inhibitors (MAOIs) | •• | ••• | •• | •• | ••• |
| Melatonergic (agomelatine) | • | • | • | • | • |
•• Some limitation
••• Marked limitation
† There is little variation in the severity of adverse effects within classes of antidepressants (but patients may differ in the adverse effects they experience). One exception is the withdrawal symptoms following discontinuation of SSRIs. There is an absence of withdrawal symptoms for fluoxetine but very severe withdrawal symptoms for paroxetine.
Matching the Antidepressant to the Clinical Presentation
Symptom-Specific Antidepressants: Antidepressants can be chosen based on the patient’s specific symptoms.
Adverse Effects Targeting Symptoms: Adverse effects of antidepressants can be used to target specific symptoms.
- Mirtazapine:
- Sedating, suitable for patients with significant insomnia.
- Associated with weight gain, useful for major depression with significant weight loss.
- Vortioxetine: Benefited patients with major depression and marked cognitive deficits in short-term trials.
Symptom Profile and Depression Subtype: Choice of antidepressant depends on the patient’s symptom profile and specific subtype of depression.
- Anxiety and Comorbid Anxiety Disorder:
- Many patients with major depression in primary care also have significant anxiety symptoms or a comorbid anxiety disorder.
- Preferred Antidepressant: SSRI.
- Melancholic Depression:
- Characterized by vegetative symptoms and psychomotor changes (agitation or retardation).
- Preferred Antidepressants: Dual-action antidepressants, such as tricyclic antidepressants or duloxetine.
- Neuropathic Pain Conditions:
- Tricyclic antidepressants or duloxetine may be used for patients with pain and associated depression.
- Dose Considerations: Higher doses are required to treat major depression compared to adjunctive therapy in pain management.
- Symptom-Specific Choices: Anxiety, weight loss, sleep disturbance, sexual dysfunction, melancholia, pain, cognitive difficulties.
- First Choice:
- SSRI for anxiety
- mirtazapine for weight loss and insomnia
- agomelatine for sexual dysfunction
- SNRIs for melancholia
- vortioxetine for cognitive difficulties
Symptoms and initial antidepressant choice
| Symptoms | Preferred antidepressant |
| Anxiety | Selective serotonin reuptake inhibitors Moclobemide |
| Weight loss, reduced appetite | Mirtazapine Mianserin |
| Sleep disturbance, insomnia | Agomelatine Mirtazapine Mianserin Tricyclic antidepressants |
| Sexual dysfunction | Agomelatine |
| Blunting, anhedonia, demotivation | Selective serotonin reuptake inhibitors Serotonin noradrenaline reuptake inhibitors Agomelatine Monoamine oxidase inhibitors Reboxetine |
| Melancholia, severe depression | Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Vortioxetine Monoamine oxidase inhibitors |
| Pain | Duloxetine Tricyclic antidepressants |
| Cognitive difficulties | Vortioxetine |
Safety Considerations
- Suicidal Thoughts: Avoid prescribing large quantities to suicidal patients.
- Drug Interactions: Consider potential interactions with other medications.
- Comorbid Conditions: Be cautious of conditions that may increase the risk of adverse effects.
- Familiarity with Antidepressants: Use a few well-known antidepressants to limit potential interactions.
Patient Preference
- Adherence: Improved if the patient is involved in the treatment decision.
- Discussion: Benefits and adverse effects should be clearly communicated.
- Address Misinformation: Provide accurate information to counteract any misinformation about antidepressants.