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CPD 42: DEPRESSION Biography - Rebecca Kate Kilfeather graduated with a BSc Hons Biological Science and a Master of Pharmacy in The Robert Gordon University, Aberdeen in 2011. She completed her pre-registration year in The Royal Infirmary Edinburgh in 2012, taking in rotations in the Sick Kids Hospital Edinburgh and the Chalmers Sexual Health and HIV clinic in Edinburgh. Upon moving back to Ireland Rebecca worked with Pharmaconex locuming in Dublin. Currently Rebecca is working in Perrystown Pharmacy. She was recently nominated for young pharmacist of the year 2013. 1. REFLECT - Before reading this module, consider the following: Will this clinical area Educational distance be relevant to my practice. 2. IDENTIFY - If the answer is no, I may still be interested in the area but the article may not contribute towards my continuing professional development (CPD). If the answer is yes, I should identify any knowledge gaps in the clinical area.

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Chronic Pain – assessment and management in primary care

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Treating depression in the pharmacy

60 Second Summary

Globally Sheehan et al reported in 1996 that the estimated cost of depression is a pain for 95 patients to the Irish Health Services when added mental disorder Pain is one of the commonest reasons for patients to seek that to the amount ofaffects Socialmore Welfare payments received and 1 than 350 million medical attention. A recent survey has shown that as many the lost earnings of of each patient amounted to 1.9 million people all ages. as 8.3 visits per year to primary care physicians in Ireland 6 pounds at the time of referral. The recent data from PRIME There are differing were due to symptoms of pain.2 A large scale survey carried survey that theofmean cost per chronic pain patient prescribing antidepressants. It can be seen thatshowdegrees INTRODUCTION depression out in 15 European countries and Israel in 2006, screening can cause a across all grades of pain, the burden of depression and mental health is estimated which at €5,665 per year Depression encompasses a wide range of 46,394 respondents reported that the prevalence chronic5,6 person to suffer greatly and problems are on the riseofglobally. which was extrapolated to €5.34 billion or 2.86% of Irish mental health problems,pain characterised by to severe intensity in adult Europeans was impact their daily activities. This of moderate 7 It is always difficult to estimate the exactGDP per year. can place a burden on society.6 a loss of interest and enjoyment in ordinary This demonstrates an urgent need for cost 3 number of people suffering from depression as strategies to manage chronic pain effectively. things, low mood and a 19%. range of emotional, effective Women are more likely to suffer from

Introduction

many people do not get help or are not formally physical and behavioural symptoms.1-4 It is depression, however men are more likely to More recent survey data from anotherwith study, out5 The World Health diagnosed thecarried condition. different from the common experience of feeling commit suicide which may be due to men Assembly resolution in May 2012 called for a unhappy or miserable for short people period of in a2,019 with chronic pain and 1,472 primary Understanding chronic painhelp for depression. being less likely to seek 5 coordinated and comprehensive response to degrees of depression time. There are differingcare physicians across 15 European countries, have 6 mental disorders at a country level. core symptoms classifinormal ed as healing Chronic painThe is defined as pain can thatbe outlasts that can be distinguished by mood changes. demonstrated that chronic pain affects 12-54% of adult low mood, fatigue, and lack of interest or Depression is strongly associated with cognitive It can be seen that women are more likely time three to six months), and is most frequently to (usually enjoyment in things. Europeans, andmemory its prevalence in Ireland is up to 13%.2 The abnormalities, suicidal events, impaired suffer from depression than men, with 1 associated in 4 with musculoskeletal disorders such as low 13 and action. PRIME (Prevalence, Impactwomen and Cost of Chronic Pain)for study, Depression can be further classified depending requiring treatment depression at

back pain and arthritis. However, it can also be associated

on severity as mild, moderate or severe.14 one point in their lives, compared to 1 in 10 the other hand, determined the prevalence of chronic Depression is a commononmental disorder, with other disorders such as depression or metabolic men, however 4 men are more likely to commit with more than 350 million people ages pain to be of asall high as 35.5% in Ireland. The PRIME study The management of depressive disorders or frequently neurologicinvolve conditions such aseither multiple suicide, which may be because men aredisorders less be adesigned serious health suffering globally.6 It canwas drug therapy alone or to investigatelikely the to prevalence offorchronic pain Depression seek help depression. in combination with other therapies. sclerosis. problem, especially when it is long-lasting with 5 in Ireland; compare the psychological and physical health can affect people of any age including children. severe or moderate intensity. This can cause Psycological treatments include cognitive

profiles thosetheir with and without chronic pain; and explore the person to suffer greatly and of impact Pain (acute or chronic) can be categorised nociceptive DIAGNOSIS behavioural therapy, interpersonalas therapy, 4 daily activities such as school, work and family. pain-related disability. Responses to survey questions were problem solving therapy and counselling these or neuropathic. Nociceptive pain is caused by an active Depending on the severity of the disorder, it It may even lead to suicide, whichfrom results in anpeople. are generally well accepted by patients. obtained 1,204 illness, injury and/or inflammatory process associated with 6 can be classified as mild, moderate or severe. estimated 1 million deaths per year. Regardless of the severity, symptoms should The various available have actualbeor potential tissueantidepressants damage i.e. Nociceptive pain Despite magnitude of the problem, chronic pain is There are effective treatments forthe depression, different modes of action, side effect profile present for two or more weeks. results from activity in neural pathways secondary to actual although fewer than halfboth of those affected in the and undertreated in primary care.2,5 and monitoring. The decision on the choice of under-recognised There are two main diagnostic criteria which are or potential tissue damage. Nociceptive pain mediated antidepressant should be based on is the patient world receive such treatment. There are various Indeed, up to 38% of patients beingdepression. inadequately usedreported to diagnose The International individual requirement. barriers in getting effective care including by pain receptors located in skin, musculoskeletal system, 2 Classification of DiseasesIn(ICD-10), which is a managed in primary their pain symptoms. lack of resources, lack of trained health care care for 8 bone, and joints. Neuropathic on experienced the other hand, Withdrawl symptomspain, can be WHO of mental addition, people painclassification reported waiting up toand behavioural professionals, inaccurate assessment andwith chronic when discontinuing treatments such as upset results from direct injury to a peripheral or central sensory disorders. Alternatively, a Diagnostic and social stigma. stomach, flu like symptoms, anxiety, dizziness, 2.2 years between seekingStatistic help andManual diagnosis, and 1.9 of mental disorders (DSM-IV) nerve; the affected nerves do not produce transduction and vivid dreams. Sometimes the effects can at 2 before theirthe pain wasisadequately managed. Correct diagnosis is vitalyears as occasionally produced and favoured by the American 8 mild however it depends on the patient. be nociceptors. Pain characteristics and associated conditions disorder can be misdiagnosed, resulting in Psychiatric Association. The extent of for both types of pain are shown in Table 1.

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sionals in Ireland

anagement in primary care

ehan et al reported in 1996 that the estimated cost of n for 95 patients to the Irish Health Services when added he amount of Social Welfare payments received and lost earnings of each patient amounted to 1.9 million nds at the time of referral.6 The recent data from PRIME vey show that the mean cost per chronic pain patient stimated at â‚Ź5,665 per year across all grades of pain, symptoms present is crucial in determining the ch was extrapolated to â‚Ź5.34 billion or 2.86% of Irish severity of depressive illness and helps as a 7 5,6 cost P per year. This demonstrates an the urgent need for guide on the treatment for individual. ctive strategies to manage chronic pain effectively.

Core symptoms can be classified as low mood, fatigue and lack of interest or enjoyment in things. Other symptoms derstanding chronic paininclude weight loss or gain, insomnia/hypersomnia, psychomotor feeling worthless/guilty, onic painagitation/retardation, is defined as pain that outlasts normal healing reduced concentration/indecisiveness and e (usually three to six months), and is most frequently thoughts of suicide. Core symptoms would ociated with musculoskeletal disorders as low normally be present most of thesuch time over a twoarthritis. week period for major to be k pain and However, it candepression also be associated diagnosed. Both require h other disorders such as diagnostic depressionsystems or metabolic at least one (DSM-IV) or two (ICD-10) core orders orsymptoms neurologictoconditions such as multiple be present. For major depression rosis. the DSM-IV system requires a score of five out of nine on symptoms. Patients who do not fit all chronic) the criteria have minor depression or chronic n (acute or can be categorised as nociceptive low Nociceptive mood.6 europathic. pain is caused by an active

AND AETIOLOGY ss, injuryPATHOPHYSIOLOGY and/or inflammatory process associated with ual or potential tissue damage i.e. Nociceptive Depression is a complex disorder and pain ults from itactivity in neural pathways secondary is possibly influenced by genetic and to actual It is thought there otential environmental tissue damage.factors. Nociceptive pain isthat mediated is an association with the serotonin transporter pain receptors located in skin, musculoskeletal system, gene. However, the relationship between 8 e, and joints. Neuropathic pain, is onprobably the othervery hand, genetics and depression complex andto not fully elucidated. Environmental ults from direct injury a peripheral or central sensory factors such asdo stress are main transduction contributory at ve; the affected nerves not produce factors.13 iceptors.8 Pain characteristics and associated conditions both types of pain are shown in Table 1.

There is a hypothesis that suggests a deficiency in monaminergic neurotransmission in the brain mediated by serotonin and noradrenaline. Given that reduced serotonin levels do not cause depression in all people, it is unclear if decreased serotonin synthesis is the cause or a consequence of depression.6,13 It is thought that disturbed receptor signalling, decreased sensitivity of 5-HT auto receptors, which regulate serotonin function have been associated with depression. It can also be noted that modulation of noradrenaline release by feedback inhibition was increased in depressed patients. Moreover altered receptor signalling could also be as a result of a malfunctioning of G-protein, which may also alter or impair neurotransmitter function.13 However, only 50%-70% of patients respond to these drugs, which may indicate a more complex mechanism for depression. Dopamine deficiency has also been associated. This is supported by the antidepressant activity of dopamine reuptake inhibitors and dopamine agonists. MANAGMENT When diagnosed, mild depression may improve by itself and progress monitored, known as watchful waiting, and antidepressants are not

normally recommended as first line treatment. A GP may recommend self help books or cognitive behavioural therapy. Chronic mild depression, which last two years or more is more common in the over 55 years and sometimes antidepressants are prescribed.13 However, for severe depression, the patient may require a combination of an antidepressant and talking therapy or cognitive behavioural therapy. Mental health teams made up of psychologists, psychiatrists, specialist nurses and occupational therapists provide intensive specialist treatments.14 PHARMACOTHERAPY The management of depressive disorders frequently involves drug therapy, either alone or in combination with other therapies. Psycological treatments include cognitive behavioural therapy, interpersonal therapy, problem solving therapy and counselling. These are generally well accepted by patients. Many of these can also be effective in minor depression where drug therapy would not be recommended due to the low risk benefit ratio. SIGN guidelines give reliable recommendations on these alternatives.1-4 The various antidepressants available have different modes of action, side effect

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CPD 42: DEPRESSION

profile and monitoring. The decision on the choice of antidepressant should be based on the patient's individual requirement. Traditional pharmacotherapy includes trcyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) and newer selective reuptake inhibitors (SSRIs), all of which are the first line treatment.

MAOIs

(sexual dysfunction, weight gain) and suicidal behaviour.14 These inhibit and reduce monoamine SSRIs degradation. They are used much less frequently than TCAs and SSRIs due to the SSRIs block the reuptake of serotonin in1 Module dangers of dietary and drug interactions. presynaptic neurones, the major Juneproblems 2012 with Response to MAOI treatment may take up their use are nausea and vomiting. Bleeding to three weeks or more to become maximal. disorders, due to serotonin reuptake inhibition Phenelzine, isocarboxazid and tranylcypromine has been reported. Stopping these drugs is Most people with moderate to severe are irreversible nonselective inhibitors, their often associated with withdrawl symptoms. Educational distance learning content for healthcare professionals in Ireland depression benefit from the use of effect can persist for weeks until regeneration They are relatively safe in overdose, so they antidepressants. However, people respond of monoamine oxidase. The use in traditional can be recommended in suicidal patients. The differently to antidepressants. It may take therapy is decreasing due to their serious balance of the benefits and risks in treatment two or more treatments before a patient finds side effects. For example, acute hypertensive in the under 18 years shows that SSRIs what works for them because side effects vary reactions after consumption of tyramine citalopram, paroxetine, sertraline, mirtazapine between people and treatments. rich foods such as mature cheese. Also and venlafaxine have higher harmful outcomes. drug interactions are equally serious, such There is very little in the difference in efficacy These may be started under specialist as interactions with narcotic medication, when it comes to choosing an antidepressant. supervision where there is clinical need. pseudoephedrine and SSRIs. Newer MAOIs However, the choice should be based on the However, the exception is fluoxetine. Clinical act by reversible inhibition of monoamine. An individual patient requirement, presence of trials have shown this to be effective in children example of this is moclobemide. This does not concomitant disease, existing therapy, suicide and in adolescents. SSRIs should be used require such strict dietary restrictions; however risk and previous response to treatment. It in caution in patients with epilepsy, cardiac it still has a risk of drug interaction for example must also be considered that it may take up disease, diabetes and bleeding disorders. The 1-4,13 ephedrine and pseudoephedrine. to two weeks for the antidepressant to take side effects of SSRIs include GI effects, weight effect. Also, it should be recognised that loss, hypersensitivity reactions and suicidal TCAs during the first few weeks there may be a risk of behaviour.14 The mechanism of action of TCAs involves anxiety, agitation and suicidal behaviour. Where OTHER ANTIDEPRESSANTS noradrenaline and serotonin inhibition. They necessary the patient should be monitored, are rapidly absorbed and highly plasma bound particularly in the beginning and if the dose is New antidepressants such as venlafaxine, and they have large volume of distribution. changed.14 mirtazapine and nefazodone are known as SNRI They are primarily metabolised by CYP450 Sheehan et(serotonin al reported in 1996 that the estimated cost of Introduction norepinephrine reuptake inhibitors). It should be noted that as anxiety is often enzymes and are renally excreted. They can These can be more effective than an SSRI pain for 95 patients to the Irish Health Services whenbut added present in depression and may be the interact with for SSRIs by thetoinhibition of the Pain is one of the commonest reasons patients seek they can cause a rise in blood pressure. presenting symptom, the use of anxiolytics CYP450 isoenzymes. They are used lessto the amount of Social Welfare payments received and 1 medical attention. A recent survey has shown that as many or antipsychotics may mask the diagnosis. frequently, due mainly to their adverse effects, In severe depression the lost earnings of each patienttreatments, amounted to 1.9 million Therefore, these should as be 8.3 used in caution in to primary visits per year in Ireland whichcare limitphysicians the dose that can be tolerated. They electroconvulsive therapy may be advised, it 6 pounds at the time of referral. The recent data from PRIME depression, although they aredue useful in agitated of pain. also 2pose a potential problem of toxicity in an were to symptoms A large scale survey carried is only used when antidepressants or other 14 survey show that the mean costbeen per successful. chronic painHowever, patient patients. overdose; therefore limited quantities should treatments have not out in 15 European countries and Israel in 2006, screening is estimated at €5,665 per year across all grades of pain, be prescribed at any one time. Due to the long it is linked with unpleasant side effects, such Hyponatraemia can be associated with 46,394 respondents reported that the prevalence of chronic half life, this allows for once daily administration short term to headaches, memory problems, which was as extrapolated €5.34 billion or 2.86% of Irish antidepressant treatment, especially with 13 Europeans was pain of moderate to severeusually intensity adult at in night. muscle aches and nausea. 7 SSRIs, patients, who present with drowsiness, GDP per year. This demonstrates an urgent need for cost 3 19%. confusion or convulsions but they should There are various side effects with the use Lithium may also bechronic prescribed no response effective strategies to manage painif effectively. be monitored. Patients should be monitored of TCAs, including cardiovascular (such as has been obtained from other medication. every 1-2 weeks during More the start of treatment recent survey data from another study, out nervous arrhythmias, heart carried block) central Lithium must build up in the system and a and treatment should beincontinued for four 2,019 people with chronic pain and 1,472 primary confusion) Understanding system (anxiety, dizziness, therapeutic level achieved. chronic pain Toxicity must also weeks (six in the case of the elderly) before be monitored. Therefore, regular blood tests are antimuscarinic (dry mouth, blurred vision, care physicians across 15 European countries, have considering switching due to lack of efficacy. is defined asthree pain months. that outlasts normal healing required every Salt restrictions constipation, urinary retention) endocrineChronic pain demonstrated that chronic pain affects 12-54% of adult If the patient partially responds, continuing time (usually three to six months), and is most frequently treatment for a further 2-4 weeks should be prevalence in Ireland is up to 13%.2 The Europeans, and its associated with musculoskeletal disorders such as low considered.5,14 PRIME (Prevalence, Impact and Cost of Chronic Pain) study,

Chronic Pain – assessment and management in primary care

Following remission, treatment shouldhand, be determined the prevalence of chronic on the other continued at the same dose at least 6 as 35.5% in Ireland.4 The PRIME study pain for to be as high months (12 in the elderly) or 12 months in designed to investigate the prevalence of chronic pain patients with co-existingwas general anxiety in Ireland; compare disorder. Patients with recurrent depression the psychological and physical health 14 should keep on treatment for at of least 2 years. profiles those with and without chronic pain; and explore

disability.4 Responses to survey questions were Failure to respond to thepain-related initial treatment of an SSRI may require aobtained dose increase or from 1,204 people. switching to an alternative SSRI or mirtazapine. Tricyclic antidepressantsDespite and venlafaxine may of the problem, chronic pain is the magnitude be considered in more severe depression. 2,5 both under-recognised Irreversible MAOIs should only be prescribed and undertreated in primary care. uptotoa 38% of patients reported being inadequately by specialists. Failing toIndeed, respond second antidepressant may require an additional managed in primary care for their pain symptoms.2 In antidepressant or an augmenting agent, addition, people with chronic pain reported waiting up to such as lithium, aripiprazole, quetiapine or 2.2only years help and diagnosis, and 1.9 risperidone. These should be between started byseeking a specialist. years before their pain was adequately managed.2

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back pain and arthritis. However, it can also be associated with other disorders such as depression or metabolic disorders or neurologic conditions such as multiple sclerosis.

Pain (acute or chronic) can be categorised as nociceptive or neuropathic. Nociceptive pain is caused by an active illness, injury and/or inflammatory process associated with actual or potential tissue damage i.e. Nociceptive pain results from activity in neural pathways secondary to actual or potential tissue damage. Nociceptive pain is mediated by pain receptors located in skin, musculoskeletal system, bone, and joints.8 Neuropathic pain, on the other hand, results from direct injury to a peripheral or central sensory nerve; the affected nerves do not produce transduction at nociceptors.8 Pain characteristics and associated conditions for both types of pain are shown in Table 1.

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sionals in Ireland must also be in place as salt can affect the lithium levels. An electrocardiogram must be performed before initiating lithium treatment.14

anagement in primary care CLINICAL CONSIDERATIONS

Withdrawl symptoms can be experienced when discontinuing treatments, such as upset stomach, flu like symptoms, anxiety, dizziness, and vivid dreams. Sometimes the effects can be mild but it depends on the patient. These withdrawl symptoms most likely occur with paroxetine and venlafaxine. The antidepressant should not be stopped suddenly if the patient has been on treatment for 8 weeks or more. The dose should be reduced gradually over 4 weeks or longer if symptoms emerge.14

with depression, such as poor motivation and concentration may contribute to non compliance. Often it is due to the side effects experienced and lack of efficacy. For successful treatment, therefore by choosing an adequate, well tolerated and effective drug with optimal formulation along with effective communication between the patient and healthcare professional is important in establishing compliance. The newer antidepressants are better tolerated and so promote better compliance. Furthermore, longer half-life and once daily dosing is favourable. TALKING TREATMENTS 'Cognitive behavioural therapy (CBT) concentrates on how the patient thinks, behaves and feels in the present.' It teaches them to challenge the negative thoughts. On the other hand, interpersonal treatment focuses on relationships and communication difficulties. Counselling is also effective because this helps the patient to think about problems and how to deal with them. Counsellors will support the patient in finding ways to deal with their issues. IN SUMMARY

There are opportunities to be gained from promoting mental health through public WITHDRAWAL/SWITCHING/STOPPING policies. By achieving better mental health, this ehan et Withdrawl al reportedofinMAOIs 1996 that theinestimated results symptom cost of in turn will contribute to the achievement and withdrawal on cessation therapy. This includes n for 95 patients to the Irish Health Services when added development of education, economic and social agitation, irritability, ataxia, movement goals. he amount of Social Welfare payments received and disorders, drowsiness, insomnia, vivid dreams lost earnings of each patient amounted to 1.9 million Depressive disorders are likely to develop from and cognitive impairment. Therefore, these should slowly. nds at the time be of withdrawn referral.6 The recent data from PRIME a vartiey of different factors including age, marital status, family breakdown, migration, vey showThe thatdanger the mean cost per chronic pain up patient of interactions can persist changing patterns of work, climate change, weeks after discontinuation of the stimatedtoattwo €5,665 per year across all grades of pain, risk of debt and substance abuse. A decrease nonselective to MAOI treatment and other of Irish in mental health can therefore impact hugely ch was extrapolated €5.34 billion or 2.86% antidepressants should not be started for two socially, economically and physically. By 7 P per year. This demonstrates an urgent need for cost weeks after stopping treatment (3 weeks if addressing these challenges, links between ctive strategies manage chronic pain effectively. startingto clomipramine or ipramine). Reversible mental health, economic performance and MAOIs have a shorter duration of action so no poverty can be understood and may help to treatment-free period is required on stopping. provide opportunities to educate and help derstanding chronic pain people. However, when starting a reversible MAOI it not be foroutlasts at least anormal week after onic painshould is defined asstarted pain that healing Therefore, there is a need for more health SSRI, or relatedand antidepressant has economic research to address mental health. e (usuallyan three to TCA six months), is most frequently been stopped (at least five weeks in the case of This may help to develop an improved global ociated with musculoskeletal disorders such as low fluoxetine). Furthermore, nonselective MAOIs architecture for mental health, which may in k pain and arthritis. However, it canatalso associated should not be started until leastbe 7-14 days turn strengthen the links between mental health after a tricyclic or depression related antidepressant has and social development, allowing people with h other disorders such as or metabolic been stopped. In addition an MAOI should mental health problems to succeed socially and orders or neurologic conditions such as multiple not be started for at least two weeks after a economically. rosis. previous MAOI has been stopped.14 REFERENCES In the case can of SSRIs,withdrawal symptoms n (acute or chronic) be categorised as nociceptive 1. NATIONAL INSTITUTE FOR HEALTH AND CLINICAL are higher with paroxetine. Symptoms include EXCELLANCE (NICE), 2009. Depression: the treatment europathic. Nociceptiveheadache, pain is caused byand an active GI disturbance, anxiety sleep and management of depression in adults. [online]. ss, injurydisturbance. and/or inflammatory with The most process commonassociated side effects, London: National institute for health and clinical excellence. Available from: http://guidance.nice.org. such astissue palpitations and disturbance ual or potential damage i.e.visual Nociceptive pain uk/CG90. can occur on abrupt withdrawal or marked ults from activity in neural pathways secondary to actual 2. NATIONAL INSTITUTE FOR HEALTH AND CLINICAL reduction of dose. Therefore, withdrawal should otential be tissue damage. Nociceptive EXCELLANCE (NICE), 2010. Clinical knowledge tapered over a few weeks.pain is mediated

pain receptors located in skin, musculoskeletal system, COMPLIANCE e, and joints.8 Neuropathic pain, on the other hand, is injury a major in the ults from This direct to obstacle a peripheral oreffective central sensory management of depression. There are various ve; the affected do not produce transduction at reasonsnerves why a patient would discontinue 8 iceptors.treatment. Pain characteristics andexperienced associated conditions The symptoms both types of pain are shown in Table 1.

summaries:Depression. [online]. London: National institute for health and clinical excellence. Available from: http: www.cks.nhs.uk/depression.

3. SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK (SIGN), 2010. Non-pharmaceutical management of depression in adults. [online] Edinburgh: Scottish intercollegiate Guidelines Network.

Available from: http://www.sign.ac.uk/guidelines/ fulltext/114/index.html 4. NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLANCE (NICE), 2010. Common Mental Health Disorders: Identificationand pathways to care.[online]. London: National Institute for health and clinical excellance. Available from: http://guidance.nice.org. uk/CG123 5. HEALTH SERVICE EXECUTIVE (HSE), 2014. Depression. [online] Ireland: Health service executive. Available from: http://www.hse.ie/eng/health/az/D/ Depression/ 6. WORLD HEALTH ORGANISATION, 2014. Depression; factsheet. [online] world health organisation. Available from: http://www.who.int/ mediacentre/factsheets/fs369/en/ 7. MEHTA, S. et al. ‘Psychosocial functioning in depressive patients: A comparative study between major depressive disorder and bipolar affective disorder.’ Depression research and treatment. Research article. Article ID 302741, 2014 8. NUTTING, P et al. ‘Barriers to initiating depression treatment in primary care practice’. J gen intern med, 2002; 17: 103-111. 9. JENKINS, R et al. ‘Social, economic, human rights and political challanges to global mental health’. Mental Health in Family Medicine 2011; 8:87-96. 10. JENKINS, R et al. ‘Health system challanges and solutions to improving mental health outcomes’. Mental Health In Family Medicine 2011;8:119-27. 11. JENKINS, R et al. ‘mental health and the global agenda: core conceptual issues’. Mental Health in Family Medicine 2011;8:69-82. 13. PEROVIC, B et al. ‘Getting the balance right: established and emerging therapies for majordepressive disorders’. Neuropsychiatric disease and treatment. 2010;6;343-364. 14. BRITISH NATIONAL FORMULARY. No 67. March 2014. BNF online www.bnf.org.uk

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