Managing Depression

Depression is very common and most patients will present and be managed in primary care. Depression is the fourth global burden of disease and the largest non-fatal burden of disease.¹ Therefore, a high index of suspicion is required. This includes being aware of the need to screen patients in high-risk groups e.g. chronic physical illness or past history of depression.

Also see full articles on Depression and Postnatal Depression.

Diagnosis of depression is based on symptoms as outlined in ICD-10 - (see our specific article on Depression). Also see NICE guidelines.²

• Full history and examination - consider organic causes of depression e.g. hypothyroidism, panhypopituitarism, drug abuse.
• Assess safety of patient to self and others - they may need to be admitted (voluntarily or as per the Mental Health Act).
• Consider whether patient needs to have treatment in secondary care e.g. severe depression, depression with psychosis.
• Assess suicidal intent at regular intervals.
• Involve patients and family members (if patient's consent). One needs to consider patients cultural background and social circumstances.
• Treatment of depression: needs to be multidisciplinary. This involves a combination of medication, psychotherapeutic and psychosocial interventions e.g. self-help groups and support groups.¹

• Mild depression - It is estimated that mild depression is twice as common as other forms of depression. Further, simple interventions such as, close monitoring with telephone contact can improve outcomes in this group.³ Treatment usually includes observation, psychoeducation and psychosocial interventions. Psychotherapeutic therapies may also be required.
• Moderate to severe depression - medication and/or psychotherapeutic treatments and psychosocial interventions.
• Treatment resistant depression - combination of treatments, including more complex psychotherapeutic interventions.
• Severe depression with risk to life - combination of treatments e.g. electroconvulsive therapy, and more complex psychotherapeutic interventions.

Starting medication

• Need an open and honest discussion with patient. Reason for therapy, possible adverse effects and risk of inadequate response should be discussed. 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.
• Consider co-morbidities and potential drug interactions before prescribing antidepressants.
• If antidepressants are used ensure patients are aware that it may take three to six weeks for an effect.
• Warn patient about initial side effects and that these abate after 4-6 weeks.

Major classes of antidepressants

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

• Use antidepressants in all except mild depression (benefit not proven). Despite NICE guidance not recommending the use of antidepressants in mild depression, some early work has reported benefits with tricyclic antidepressants (TCA).⁴
• 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.

Selective serotonin re-uptake inhibitor

Also see full article on Selective Serotonin Re-uptake Inhibitor (SSRIs).

• 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 syndrome⁵

Serotonin syndrome is 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)

A meta-analysis of a number of trials of SSRIs in children suggests that the benefits of SSRIs appear to outweigh any suicidal risks in a number of conditions including depression and anxiety disorders.⁶ Patients should be warned to seek help if they become more agitated.

If patients are at increased suicide risk:

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

Careful observation and monitoring is advised.

Tricyclic antidepressants

Also see full article on Tricyclic Antidepressants (TCAs).

• 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.

Monoamine oxidase inhibitors (MAOIs)

Also see full article on MAOIs.

• Examples include phenelzine and isocarboxazid.
• Initiated usually by mental health specialists.
• Useful in atypical depression.
• Wait two weeks after stopping MAOI before starting TCA or SSRI and vice versa.
• 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.

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

Other antidepressants

• Flupentixol (see Atypical Antipsychotics).
• Mirtazapine - 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 - See full article on venlafaxine. Venlafaxine is a serotonin and noradrenaline reuptake inhibitor. No sedation and no antimuscarinic effects, however prior to initiation need 12 lead ECG (looking for arrhythmias) and hypertension. It should generally be prescribed in specialist setting which includes GP with a specialist interest. It should not be used in patients with existing heart disease, electrolyte imbalance and hypertension. It has also been associated with symptoms on discontinuation.

Follow-up and monitoring

• Review 1 - 2 weekly at the start (more frequent if increased suicide risk).
• Continue for 4 - 6 weeks before determining if non-efficacious.
• Monitor for side effects and symptom changes.
• If partial response than continue for further few weeks.
• If an inadequate response seen or no response consider changing antidepressant.

• After patients achieve remission continue for six months prior to considering stopping.
• Reduce dose slowly 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, a high risk of recurrence or residual symptoms.
• Continue antidepressants for at least 2 years if there have been two or more previous episodes of depression.

• Assess compliance and adherence.
• Increase dose if possible.
• Consider switching after a month e.g. another SSRI, or TCA. The new antidepressant can be within the initial class of antidepressant or between classes.
• 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.

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 Mirtazapine 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.

• This includes problem solving sessions, cognitive behaviour therapy (CBT) and counselling. CBT alone maybe helpful in mild and moderate depression. However, moderate to severe depression responds to structured psychological interventions e.g. interpersonal or marital therapy.

Also see full article on Electroconvulsive Therapy.

• 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.