Depression in adults: recognition and management

Worldwide, it is estimated that 350 million people are affected by depression and it is expected to be the second leading cause of disability by the year 2020, behind ischaemic heart disease^[1]
. At its worst and left untreated, depression can lead to suicide. According to the World Health Organization, more than 800,000 people die from suicide every year and it is the second leading cause of death in young people aged 15–29 years^[1]
.

Specifically in the UK, depression is the most common mental health condition affecting up to 3% of the population per year, and one in four of the population will be affected by depression in their lifetime^[2]
. However, there are many individuals who remain undiagnosed and, therefore, do not seek treatment^[3]
. Men may be particularly affected by a lack of diagnosis or by not seeking help since male suicide accounts for 76% of all suicides in the UK and is the single biggest cause of death in men under the age of 45 years^[4]
.

Given the scale and nature of the problem, all healthcare professionals should be able to recognise the symptoms of depression in people who use their services and direct patients towards accessing treatment. This article examines how a diagnosis of depression is made, the various treatment options available (both pharmacological and non-pharmacological), looking specifically at considerations in different patient groups, self-management approaches, and the role of the pharmacy team in managing and supporting those who have symptoms of depression.

Diagnostic criteria, signs and symptoms

In order to appropriately treat depression, an accurate diagnosis and assessment of severity is required. Although there are several ways to diagnose depression, in all cases these are based on a biopsychosocial assessment^[5]
. This is a qualitative assessment of someone presenting with suspected depression that considers the various domains of symptoms, which can be physical, psychological or social. Although the International Classification of Disease 10th Edition (ICD-10) can be used, the National Institute for Health and Care Excellence (NICE) guidelines on depression^[3]
use the Diagnostic and Statistical Manual of Mental Disorders (DSM-4) criteria to standardise the diagnosis and treatment of depression. These diagnostic criteria are outlined below.

Importantly, one (or both) of the core features of depression should be present for depression to be considered an appropriate diagnosis: a low or depressed mood and a loss of interest or pleasure in activities that the person would otherwise enjoy (anhedonia). These form the basis of initial screening questions to those at risk of depression^[3]
.

For a diagnosis of depression to be made against the DSM-4 criteria, the practitioner should screen for the following symptoms. Five or more of these symptoms must have been present during the same two-week period and represent a change from previous functioning^[3]
:

• Changes in sleep pattern (insomnia is more common, but excessive sleep is also possible);
• Changes in appetite or weight (eating less leading to weight loss of more than 5% is common, but increased food intake may also occur e.g. comfort eating);
• Observable changes in activity (more commonly reduced activity);
• Feelings of guilt and worthlessness;
• Thoughts of death or suicide (which may include plans);
• Feelings of fatigue/loss of energy;
• Cognitive symptoms, such as decreased focus or concentration.

The severity of the depression is based on the number of symptoms the patient has in addition to the core symptoms. In mild depression there are few (if any) symptoms in excess of the five required to make the diagnosis, and these symptoms result in only minor functional impairment. For a diagnosis of severe depression, most symptoms should feature, and these will significantly interfere with functioning. Severe symptoms can occur with or without psychotic phenomena. Moderate depression falls between the two extremes^[3]
.

While a depressed mood is often the most prominent symptom, it may not be recognised by the person, and biological symptoms, such as constipation, fatigue, and aches and pains in the body, may precipitate a consultation with a GP. Similarly, complaints about a pre-existing medical condition worsening or medically unexplained symptoms may indicate an underlying or unrecognised depression^[3]
.

It is also important to consider that depression in older people can be manifested with poor memory, particularly in areas of recognition and retrieval of recently learned information. This is described as ‘pseudo-dementia’, whereby normal cognition returns once the depression is treated^[6]
.

Physical or chemical causes of depression should be ruled out and treated prior to a diagnosis. For example, antiepileptics or isotretinoin may cause or worsen depressive illness and low folate levels may also cause symptoms of depression. Further lists of psychiatric side effects of medicines are found in the Maudsley Prescribing Guidelines^[7]
and Psychotropic Drug Directory^[8]
. A helpful review article was also published in December 2016^[9]
.

Treatment options

Having established the correct diagnosis and severity of the depression, as with other mental disorders, NICE advises a stepwise approach to treating it based on the severity of symptoms^[3]
. See Table 1 for details for the stepped care model.

The diagnosis of depression and use of antidepressants to treat depression in children and adolescents and those who are pregnant, post-partum or breastfeeding are specialist areas outside the remit of this article^[10],
[11]
. Readers are encouraged to refer to specialist reference sources and their local mental health pharmacy team should they require advice.

Treatment of subthreshold or mild depression

Evidence-based self care and psychological therapies are indicated treatments for people with symptoms of subthreshold or mild depression.

Self-management

NICE recommends that sleep hygiene is a key intervention that should be discussed with all people experiencing depressive symptoms^[3]
. Sleep hygiene advice includes:

• Establishing regular sleep and wake times and avoiding daytime naps;
• Avoiding excessive eating, smoking or drinking of alcohol;
• Avoiding caffeine-containing products three to six hours before bed;
• Creating a suitable environment for sleep, such as sleeping in a darkened room or avoiding extremes of temperature and background noise;
• Taking regular physical exercise during the day (which may promote sleep);
• Avoiding ‘screen-time’ from back-lit screens, such as mobile devices or the television (the blue-based light emitted inhibits melatonin release).

Mindfulness-based practices such as meditation have been shown to be effective in managing symptoms of depression and reducing stress^[3]
. Conveniently, several smartphone or other mobile device apps are readily available (although apps are best avoided before bed; see above).

Pharmacological treatments

Although there is evidence that the herbal remedy St John’s Wort may be of benefit in mild or moderate depression, practitioners should be aware that there is uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)^[12]
. As such, it is not to be prescribed on the NHS. People choosing to take St John’s Wort should be made aware of the risks of this preparation and supported to use it safely, or referred to their GP for review.

In subthreshold or mild depression, antidepressants are not routinely recommended and therefore should not routinely be used. However, they may be used in people experiencing subthreshold or mild symptoms when there is a past history of moderate or severe depression, the subthreshold symptoms have been present for at least two years, or subthreshold symptoms persist after other interventions have been tried and have not been successful.

If antidepressants are prescribed, they should be used in line with the recommendations for the pharmacological treatments for moderate-to-severe depression^[3]
.

Psychological treatments

Psychological treatments are primarily indicated for those with subthreshold or mild symptoms of depression since antidepressants show little efficacy over placebo at this severity level and side effects may outweigh the benefit of medicines in less severe forms of illness.

NICE recommends that at least one low-intensity psychological intervention is offered to the patient, or group-based cognitive behavioural therapy (CBT), if the former option is declined.

Interventions recognised to be helpful include: individually guided self-help programmes over 9–12 weeks, with support in person or over the telephone; computerised CBT over 9–12 weeks; or a structured group-based physical activity programme of two to three sessions per week of moderate duration (45 minutes to 60 minutes) over three months. For those with a long-term condition, group-based peer support for 8–12 weekly sessions is also effective at managing symptoms of depression^[3]
.

NICE-approved psychological interventions are available free on the NHS and these are accessed via a GP or self-referral to the person’s local ‘Improving access to psychological therapies’ (IAPT) service^[3]
. See ‘Useful links and resources’ for further details on these services.

Given the incidence of depression and anxiety disorders, waiting lists for these services can be lengthy in some parts of the UK and may not be quickly accessible for those who may benefit from them. Furthermore, depending on the severity of the depression, people may find talking therapies difficult to engage with as a process and, in this respect, medicines may be helpful for a subset of patients.

Treatment of moderate-to-severe depression

Pharmacological treatments

Antidepressants are effective treatments for moderate-to-severe depression, and broadly, these are as effective as one another^[13]
. In terms of numbers needed to treat (NNT) in order to prevent relapse of depression, antidepressants have a strong effect with an NNT of 3.5^[14]
.

Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of antidepressant treatment because of their relatively tolerable side effect profile and safety in overdose compared with other antidepressant classes, such as tricyclic antidepressants (e.g. amitriptyline) or serotonin noradrenaline reuptake inhibitors (SNRIs; e.g. venlafaxine).

Whichever antidepressant is used to treat depression, adherence with treatment should be encouraged at optimal doses for long enough to obtain maximal benefit, including after remission of symptoms. Often, an antidepressant may be started by a person with the expectation of a rapid improvement in mood or functioning. The patient may then be discouraged from continuing with medicines where this does not occur or become poorly motivated to take medicines when no improvement is seen at a sub-optimal dose. The pharmacy team can support and promote adherence by offering reassurance around time to onset of action.

Although time to antidepressant action is often quoted as three to four weeks after initiation^[7],
[8]
, meta-analysis data indicate that symptoms of depression begin to improve within one to two weeks of taking an effective antidepressant^[13]
. The difference in these figures is likely because of the use of structured rating scales used during clinical trials, which are sensitive enough to detect improvement in the early stages of treatment. It should also be noted that adolescents and young adults (up to the age of 25 years) may be more at risk of increased suicidality, especially during the initial two weeks of treatment, and therefore they require more frequent monitoring of their symptoms at this stage^[3]
.

Antidepressants should, therefore, be taken for at least four weeks before considering their full efficacy; however, improvements are usually seen within two weeks of initiation if a person is responsive to that particular treatment^[7],
[8]
. See Box 1 for information on the minimum effective doses of commonly used antidepressants and Box 2 for general minimum treatment duration recommendations.

Once a patient goes into remission, antidepressants should be continued post-recovery to promote continued functional improvement and prevent relapse at a later date. Long-term adherence to antidepressants is associated with reduced mortality^[15]
. Suggested timeframes for continuation are shown in Box 2.

When antidepressants are stopped, a gradual reduction in dose is preferred to an abrupt withdrawal in order to attenuate potential discontinuation symptoms. Discontinuation symptoms usually appear within five days of stopping, depending on the half-life of the antidepressant, and they are more common in medicines with a short half-life, such as paroxetine or venlafaxine. Discontinuation symptoms may include flu-like symptoms, shock-like sensations, headache, insomnia and excessive dreaming. Symptoms are usually mild and self-limiting but may be perceived as being more severe, especially when patients do not have prior warning of them^[3]
.

Reassurance that symptoms will pass in a few days may be helpful in milder cases but if the experience is severe then reintroducing the medicines at the previous dosage may be helpful as well as suggesting a more gradual taper and withdrawal^[3]
.

Psychological treatments

Those suffering with moderate-to-severe depression benefit from combined psychological and pharmacological treatment. Antidepressants may enhance the effectiveness of psychotherapy with an NNT of seven^[16]
. A recent meta-analysis for CBT combined with medication shows that CBT was neither better nor worse than other treatments when used alone, but when combined with antidepressants, the combination was superior^[17]
. Although the studies were of a high quality, the effect size was small and there were signs of publication bias. Nevertheless, combined talking and pharmacological intervention is recommended by NICE and is usually acceptable to the person with depression^[3]
.

The interventions used for moderate-to-severe depression are of a higher intensity than those used in mild depression and include individual CBT, interpersonal therapy or behavioural activation. Behavioural couples therapy may be used where the person is in a relationship with a regular partner and the relationship is a possible contributing factor to the depression. If these talking treatments are declined, psychodynamic psychotherapy or counselling may be considered, although there are uncertainties about the effectiveness of these forms of talking therapy for depression^[3]
.

Antidepressant treatments in special groups

As mentioned earlier, the use of antidepressants to treat depression in children and adolescents^[10]
and those who are pregnant, post-partum or breastfeeding^[11]
are specialist areas that are outside the remit of this article. Equally, managing treatment-resistant depression or depression occurring in bipolar affective disorder^[18]
are areas of specialist practice. Readers are encouraged to refer to specialist reference sources and their local mental health pharmacy team should they require advice in these cases.

Cardiovascular disease

Depression itself may be a predisposing factor in the development of cardiovascular disease and myocardial infarction (MI)^[19]
. SSRIs, generally, are considered lower-risk agents when treating depression in those who have had an MI, with sertraline considered the safest immediately post-MI^[20]
. Of the SSRIs, citalopram is least preferred because of its dose-dependent association with QT-interval prolongation, but it may be used with caution. Mirtazapine is also considered a lower-risk option where SSRIs have been ineffective or not tolerated. The UK Medicines Information (UKMi) Specialist Pharmacy Service has a helpful summary of using antidepressants in cardiovascular disease^[21]
.

Diabetes

Diabetes is a major risk factor for depression and adequately treated depression may improve various parameters such as glycaemic control. Treatment with antidepressants may reduce weight and insulin requirements. Fluoxetine may be considered an antidepressant of choice in those with diabetes^[8]
. However, it is important to know that the side effects of fluoxetine — such as tremor, nausea, sweating and anxiety — may be mistaken for hypoglycaemia in some cases.

Multiple medicines

Although antidepressants are generally considered to be safe, it is important to be aware that interactions may occur with other prescribed medicines and that these are usually predictable. The following examples are not exhaustive and readers may find this summary article helpful to guide further reading^[22]
.

SSRIs used alone may increase bleeding times owing to decreased platelet activation, which is mediated via serotonin receptors on platelet cell bodies. When combined with other agents that affect platelet action, such as aspirin or clopidogrel, an increased risk of gastrointestinal bleeds is seen, especially in those aged over 65 years^[7]
. Anticoagulant agents such as warfarin, rivaroxaban or dabigatran will also affect bleeding times via different mechanisms and, therefore, their use is cautioned with SSRIs. Mirtazapine may be a suitable alternative in both cases.

When multiple medicines are used, there is potential for serotonin syndrome. Serotonin syndrome or toxicity results in symptoms consisting of a triad of features: alteration of mental status (agitation, restlessness), neuromuscular abnormalities (tremors, muscle rigidity), and autonomic hyperactivity (tachycardia, diaphoresis, vomiting and diarrhoea). It is a form of toxicity rather than an idiosyncratic drug reaction and can occur when multiple serotonergic medicines are used in combination or a pharmacokinetic interaction causes an increase in the action of serotonergic compounds. A fuller review has been produced by UKMi^[23]
. Medicines that have serotonergic actions (other than antidepressants) include tramadol, oxycodone, lithium, linezolid, carbamazepine, valproate, triptans and chlorphenamine.

With regards to pharmacokinetic interactions, citalopram and sertraline are generally considered to have the lowest propensity for interaction via the cytochrome P450 system. However, fluvoxamine significantly inhibits CYP1A2, CYP2C and CYP3A4; increasing plasma concentrations of medicines metabolised by this route^[24]
. Fluoxetine and paroxetine also inhibit CYP2D6.

The role of the pharmacist

In 90% of cases, depression and anxiety are treated in primary care and non-specialist settings. Furthermore, out of 130 cases of depression (including those considered mild) per 1,000, only 80 will consult their GP^[25]
. Therefore, community-based primary care staff — and especially the pharmacy team — have many contact opportunities to identify those who may be suffering and offer effective interventions or signposts to other sources of help if appropriate.

Self-management approaches already discussed can be encouraged and actively promoted as part of general healthy living and well-being, as well as signposting to local or online support groups that may be supported by organisations such as Mind (see ‘Useful links and resources’). The pharmacy team could assist patients in self-referral to the local IAPT service and forge links with these organisations.

When antidepressants are indicated, there are great opportunities to optimise medicines use. Prescribers should be encouraged to titrate doses of antidepressants to at least minimum effective doses through prescription review.

The pharmacy team can also support the patient’s adherence by using their skills and knowledge to manage a patient’s expectation of medicines, offering motivation and support while they continue taking medicines both initially and in the maintenance phase of treatment. The pharmacy team may also help in managing side effects that may be experienced with treatment, including discontinuation symptoms previously discussed.

Common side effects of antidepressants are often easily managed in a non-specialist setting. For example, advising a patient that: if they are feeling sick, then take the medicines with food; take a sedating medicine at night rather than during the day time; take a stimulating medicine in the morning. Reassurance about side effects and instilling a sense of hopefulness should the medicine not be immediately effective can be significant interventions to patients taking any medicines, not necessarily just those taking antidepressants.

The pharmacy team may also wish to make contact with their local community mental health team or mental health pharmacists to build links, further signpost their patients to these services, or get specialist advice or further clinical support in managing the medicines of those people they see regularly.

Summary

Depression is a common mental health problem that all healthcare professionals will come into contact with, especially those in primary care. Less severe forms of depression are best treated with talking therapies, while more severe forms require pharmacological treatments with or without talking therapies. SSRI antidepressants are considered first-line options when pharmacological treatments are required and should be taken at minimum effective doses, at least, to treat and maintain recovery. Pharmacists can support and advise patients on effective self-care treatment options as well as optimise the use of any prescribed treatments.