Managing Depression

1. Majority of depressed patients will present to and be managed in primary care.
2. Therefore, need a high index of suspicion and need to screen patients in high-risk groups e.g. chronic physical illness or past history of depression.

For postnatal depression see separate article.

Diagnosis of depression is based on ten symptoms outlined in ICD-10. Also see NICE guidelines.¹

• Mild depression (four symptoms) - antidepressants not recommended, monitor and reassess in two weeks
• Moderate depression (five to six symptoms)
• Severe depression (seven or more symptoms)
• Severe depression with psychotic symptoms

• Full history and examination - consider organic causes of depression e.g. hypothyroidism, panhypopituitarism.
• Assess safety of patient to self and others - they may need to be admitted (voluntarily or as per the Mental Health Act).
• Assess suicidal intent at regular intervals.
• Involve patients and family members (at patients consent). Along these lines need to consider patients cultural background and social circumstances.
• Self-help groups and support groups.

• Need an open and honest discussion with patient and agree to medication. If patient not keen then reassess in two weeks.
• If you suspect poor insight due to depression then refer to a mental health specialist. May need to be urgent.
• Consider psychological interventions in all patients e.g. cognitive based therapy, relaxation therapy.
• If antidepressants are used ensure patients are aware that it may take three to six weeks for an effect.

• Tricyclic and related antidepressants.
• Selective serotonin re-uptake inhibitors.
• Monoamine oxidase inhibitors.
• Others e.g. Venlafaxine.

Antidepressant medication

• Use antidepressants in all except mild depression (benefit not proven).
• Selective serotonin re-uptake inhibitors (SSRIs), are first line and just as effective as TCA.
• Careful and continuous monitoring of side effects, symptom resolution and suicidal ideation.
• Continue for 6 months after remission - then review on a regular basis.
• Venlafaxine, dosulepin, phenelzine and lithium should only be initiated by specialist mental health professionals.

• Fewer antimuscarinic side effects therefore better tolerated.
• Less cardiotoxic in overdose (compared with TCA).
• Less sedating.
• SSRIs not proven to cause tolerance or craving, but some patients do develop symptoms on stopping or dose reduction (e.g. headache, nausea and anxiety).
• May lead to hyponatraemia (may be due to SIADH).
• Avoid in epilepsy, cardiac disease, hepatic and renal impairment.
• May impair performance of skilled tasks.
• Nausea and vomiting are common.
• Associated with bleeding disorders.

Serotonin Syndrome²

A potentially life threatening situation resulting from excessive serotonergic activity.
Consists of a triad:

• Altered mental status
• Neuromuscular abnormalities e.g. rigidity, hyperreflexia, clonus and seizures
• Autonomic dysfunction e.g. labile BP, tachycardia, sweating

More common when two SSRIs given together, but can occur with a single SSRI.

SSRIs and suicide

SSRIs have been associated with suicidal ideation in

• Patients at increased risk of suicide,
• Young patients (under 30 years of age).

If patients are at increased suicide risk:

• Assess weekly until patient stable (may need telephone contact)
• Provide limited supply of tablets
• Extra support

• Poorly tolerated in comparison to the SSRIs
• However, tricyclic related drugs e.g. trazodone have a lower incidence of antimuscarinic side-effects
• Increased risk of cardiotoxicity (lofepramine lacks this).
• TCAs are dangerous and still a major cause of death when taken in overdose
• Perform ECG and record BP prior to treatment
• Associated with neuroleptic malignant syndrome

1. Examples include phenelzine and isocarboxazid
2. Initiated usually by mental health specialists
3. Useful in atypical depression
4. Wait two weeks after stopping MAOI before starting TCA or SSRI and vice versa
5. Inform patients of important interactions:

   MAOIs inhibit monoamine oxidase which leads to an accumulation of amine neurotransmitters. Indirect acting sympathomimetics enhanced e.g. cough and decongestant preparations. Effect of tyramine enhanced e.g. in marmite?, mature cheese and pickled herring. Avoid stale food especially meats and fish. Avoid offal. Results in dangerously high BP, which may be fatal - early symptom is a throbbing headache. Effect of interactions persists up to two weeks after discontinuing MAOIs.

6. Monitor blood pressure
7. Suddenly stopping not advised - associated with GI symptoms, headache, dizzy spells and insomnia and possibly panic attacks and motor restlessness

• Flupentixol (see atypical antipsychotics).
• Mirtazepine - a presynaptic alpha 2 receptor blocker. Can cause sedation - but fewer antimuscarinic effects.
• Reboxetine - selective inhibitor of noradrenaline. May improve social functioning.
• Tryptophan - useful in some cases of resistant depression. Associated with eosinophilia-myalgia syndrome.
• Venlafaxine - serotonin and noradrenaline reuptake inhibitor. No sedation and no antimuscarinic effects. CSM advice that should only be initiated by specialist in mental health and not in heart disease, electrolyte imbalance and hypertension.

1. Review 1 - 2 weekly at the start (more frequent if increased suicide risk).
2. Continue for 4 - 6 weeks before determining if non-efficacious.
3. If partial response than continue for further few weeks.

• Assess compliance
• Increase dose if possible
• Consider switching after a month e.g. another SSRI, mirtazepine, moclobemide, reboxetine or TCA
• If a new antidepressant is started gradually increase the dose and watch for the serotonin syndrome (if changing from one SSRI to another see above)
• If failure to respond to second antidepressant - refer to specialist who will consider use of other agents e.g. lithium, electroconvulsive therapy

• After patients achieve remission continue for six months prior to considering stopping.
• Reduce dose over four weeks - watching for relapse.
• However, have a low threshold for continuing antidepressant medication in certain patients e.g. with previous episodes of depression or residual symptoms.
• Continue anti depressants for at least 2 years if there have been two or more previous episodes of depression.

Atypical depression

• Presents with mood reactivity, over eating and over sleeping.
• More frequent in females and younger age.
• Refer to mental health specialist - SSRI usually used.
• Phenelzine has also been used.

Chronic depression

• Patients have diagnostic criteria of depression for at least 2 years.
• Associated with disability from psychosocial dysfunction.
• Usually requires specialist treatment with a combination of anti depressants.
• SSRIs are again first line.
• Will need psychological interventions and possibly a rehabilitation programme.

Treatment resistant depression

• Defined by NICE as " ... depression ... which fails to respond to two or more antidepressants given sequentially at an adequate dose for an adequate time".
• Refer to mental health specialist.
• Treated with a combination of antidepressants e.g. SSRIs and mirtazepine and cognitive based therapy.
• Lithium or venlafaxine can also be used.
• Phenelzine can be used in those who are capable of managing dietary restrictions and side effects.

• Only for rapid and short-term improvement of severe symptoms e.g. life threatening depression.
• Need to assess risk-benefit for individual patient.
• Associated with short term cognitive impairment.
• Increased risk in elderly, children and pregnant females.
• Valid consent should be obtained if possible.

• Antidepressants are still a major cause of death - 80% are attributed to suicide.³
• TCAs are most toxic of all the antidepressants, particularly amitriptyline and dothiepin. Lofepramine is associated with a lower incidence of mortality.
• SSRIs taken alone in overdose are less likely to cause death.
• Mortality with SSRIs occurs more when combinations of SSRI are used with TCA.³
• Drug overdose with antidepressants are more common in patients with drug misuse e.g. opiates and alcohol.
• Monitor suicide risk carefully.
• Any suspicion of overdose refer urgently to the nearest accident and emergency department.