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Treatment recommendations differ between mild, moderate and severe depression
Severe depression is usually marked by agitation or retardation and the patient may be
reluctant or unable to describe other features in detail. Both social functioning and work
performance are likely to be disrupted. (PHQ scores of > 20) Severe depression
requires anti-depressant medication and consideration of Referral to
Mental Health Specialists. Risk assessment is essential. Reviewing Progress
Patients are more likely to implement advice if they know the GP will see them again soon to
check whether the advice has been implemented or was helpful.
Contact at fortnightly intervals for moderate depression and initially weekly in severe
depression should be considered, with contact remaining at 2-3 months intervals throughout
treatment. Referral to Mental Health Specialists
Psychiatrists are happy and willing to see all patients with depression or any other psychiatric
disorder if the general practitioner feels this necessary and outlines the reasons for
requesting a psychiatric opinion in the referral letter. Guidelines for consideration as to what
and when to refer include:
• Severe depression often with psychotic ideation where admission to hospital may be
• Where there is suicidal ideation and you consider the patient to be at risk
• Failure to respond to treatment with at least one antidepressant drug despite
adequate dosage and duration of treatment
• Chronic illness where the GP wishes advice as to continued management
• Where management is difficult or stressful and the GP feels in need of support or a
• Where the GP wishes advice as to referral to other areas of the service
• At the patient’s request if the GP feels this is appropriate
Community Mental Health Services
The structure of the Community Mental health Services varies throughout the Highlands and therefore there are local arrangements in place for referrals. Teams may compromise of Social Workers, Occupational Therapists and Community Psychiatric Nurses. They can offer a range of core skills such as assessment, treatment and care, outcome evaluation and health education. Some teams have specialists in Cognitive Behavioural Therapy. Community Mental Health Teams will consider referrals for any patient who is or is suspected to be suffering depression.
Consider referral to Community Mental Health if the patient:
Ø Is aged 16 or over and has left school Ø Is isolated and vulnerable Ø Has a previous history of mental health problems Ø Has thoughts of self harm and/or feelings of hopelessness Ø Abnormal grief reaction
Ø Presents with multiple psychosocial problems Ø Has a history of poor coping skills
Referral to Cognitive Behaviour Therapists
CBT is particularly suitable for those who
• Can not or do not wish to take drugs
• Experience hopelessness and feelings of helplessness
Development plans for Psychological Therapies across Highlands include the establishment
of Cognitive Behaviour Therapists posts for each area. These should be coming on stream
during the lifetime of these Guidelines. Referral to Psychology
Psychologists accept referrals of patients with all forms of depressive difficulties for
assessment and treatment. Psychological therapy may be particularly relevant when one or
more of the following apply:
Duration of six months in spite of adequate drug therapy
Refusal to use antidepressants/failure to respond to medication/other factors preventing drug treatment
Concurrent/alternative diagnosis or difficultly, particularly anxiety disorders, self injury
Depression is part of a pattern of difficulties arising out of adverse or traumatic early life experiences
In order for patients to see a psychologist they need to be able to attend a clinic during working hours.
Drug T herapy-
Antidepressants in Pregnancy and Breast-feeding
Patients with low mood or loss of interest plus at least four of the other diagnostic features
mentioned are most likely to respond to drug treatment. For these patients with moderate to
severe depression, antidepressants should be considered the mainstay of treatment.
Antidepressants are effective in the treatment of moderate to severe depression. However,
antidepressants do not appear more efficacious than placebo in milder depression and are
not recommended for the initial treatment of mild depression. In milder depressive states
non-drug strategies are often preferable to drug treatment.
The fact that a patient’s depression is “understandable” should not deter the GP from
prescribing antidepressants since they are just as likely to be effective. 70% of patients are
likely to respond to the first intervention offered. Antidepressant Treatment – Which Drug to Use
All antidepressants have broadly similar efficacy (Song et al 1993) and therefore the choice
of drug for a particular patient will depend on the nature of the symptoms, side-effect profile,
concomitant therapy, concurrent illness, patient preference and safety in over-dose.
Previous response to treatment is also a strong indication to repeat that treatment in future
The antidepressant whose profile best fits the ideal for an individual patient should be
prescribed. In the absence of special factors, choose antidepressants which are better
tolerated, safer in overdose, and more likely to be prescribed at effective doses. Since there
is most evidence for SSRIs, they should be regarded as the preferred option for first line use.
When prescribing an SSRI, fluoxetine is a reasonable choice as it has efficacy similar to
other SSRIs, but is available as a generic, and hence provides additional benefit in terms of
When considering toxicity in overdose, the evidence to date suggests that SSRIs, newer
tricyclics, mirtazapine and reboxetine are safer than older tricyclics or venlafaxine.
The newer agents may have a place in treatment of patients for whom first choice drugs are
poorly tolerated or ineffective.
The cost of these drugs should also be taken into account when a decision is made to
prescribe, especially when choosing between drugs in the same class.
Antidepressants account for a large proportion of the primary care drugs spend.
TCAs are by far the cheapest agents, especially compared to newer antidepressants, but
they carry the risk that they may be prescribed in sub-therapeutic doses, e.g. to avoid
adverse effects which are common with TCAs. Generic SSRI preparations such as
fluoxetine offer a safer but relatively inexpensive alternative. The Elderly
The same principals apply to the elderly as the adult population in the decision on which
antidepressant to use. Concomitant therapy and concurrent illness are likely to be of greater
The main differences in the elderly regarding the use of antidepressant drugs relate to
altered distribution, metabolism and excretion and their increased sensitivity to the effects of
these drugs. This provides the reasoning behind the adage “start low and go slow” with
antidepressant doses in this population. Psychomotor impairment and postural hypotension
are particularly problematic in the elderly and there is therefore an argument for generally
avoiding the older tricyclics (Lasser et al 1998). Starting Treatment
SSRIs can usually be started at a therapeutic dose.
TCAs should be gradually increased to the therapeutic dose over 1-2 weeks, or as quickly as
can be tolerated.
Patients should be advised of the likely early side effects, and the lag time before symptoms
Increased anxiety/agitation can be problematic at the early stages of treatment with an SSRI.
Judicious short-term use of a benzodiazepine may be helpful in such situations. CSM Advice Hyponatraemia (usually in the elderly and possibly due to inappropriate
secretion of antidiuretic hormone) has been associated with all types of
antidepressants and should be considered in the differential diagnosis of all patients
who develop drowsiness, confusion or convulsion while taking an antidepressant
Compliance with prescribed medication for all chronic conditions is estimated at 50%. There
are a variety of reasons why patients cannot or will not comply with their prescribed
medication, but there are particular reasons why compliance may be a problem with
• High incidence of side effects, particularly occurring prior to the onset of
• Reluctance to accept the diagnosis of depression
• Fear that antidepressant medication is addictive
• Symptom improvement leading to patient stopping drugs, with subsequent relapse
• Difficulty obtaining relevant information
Before starting treatment compliance can be improved by
• Give positive advice regarding the benefits of treatment
• Reinforce that antidepressant are not addictive
• Inform patients about potential side effects
• Reinforce the importance of not discontinuing treatment before or during the
• Inform the patient about the possibility of discontinuation symptoms on missing
doses, or stopping antidepressant medication
• Reassure regarding the low risk of discontinuation problems if reduced and stopped
• That improvement may not be noticed until the patient has been on the medication for
• Advice that treatment is likely to be continued for at least 6 months from time of
Community Pharmacists are usually pleased to offer advice to patients on antidepressants.
especially in older or physically ill patients, more susceptible to side effects. They are better tolerated than TCAs and are more likely to be prescribed at adequate doses for an adequate period. (Rosholm et al 1997). Fewer anticholinergic and cardiovascular side effects than TCAs. Are not without side effects. These are mainly gastrointestinal e.g. nausea, diarrhoea.
limited by side effects. Anticholinergic side effects e.g. constipation, blurred vision and dry mouth are common. Cardiovascular effects such as arrhythmias and hypotension can also occur. TCAs can prolong the QT interval. Sedation can be problematic but may also be useful in some patients. Tolerance to some side effects can develop but may necessitate gradual dosage increases. Amitriptyline is comparable in efficacy and safety to other TCAs but is recommended, as it is more cost effective.
recommend initiation and monitoring under specialist supervision only. May have greater efficacy than SSRIs at doses of 150mg or greater. Dose responsive so can titrate dose for further effect. Side effect profile similar to SSRIs but can lower/elevate blood pressure. Note requirement for pre-treatment ECG and B.P. check.
Weight gain can be a problem. Low incidence of sexual
dysfunction. May potentiate other centrally acting sedatives. Suitable for patients who require sedation but for whom a TCA is not suitable.
with secondary care. Is not sedating but insomnia can be a problem, along with some
Normal recommended dose range for the ten most frequently prescribed antidepressants in
Highland in 2002-3 are shown below. Please see NHS Highland Joint Formulary for
currently recommended antidepressants.
*Note CSM 2004 advice. Recommended dose for depression is 20mg **Applies only to the immediate release preparation
Failure to respond despite good compliance
• No response after 4 weeks
• Partial response after 4 weeks, continue for a further 2 weeks. Partial response converted
to full response at 6 weeks? Elderly
• No response after 6 weeks
• Partial response after 6 weeks, continue for a further 3 weeks. Partial response converted
to full response at 9 weeks?
If a full response is not obtained within the time scales outlined above then:
• First increase the dose of the current antidepressant to the upper limit of the therapeutic
range, provided the patient can tolerate any side effects.
• Switch to a drug of a different class. Different classes of antidepressant in addition to
MAOIs, TCAs and SSRIs include SNRI, NARI, and NaSSAs. Call Pharmacy Department at
New Craigs Hospital for advice if required (Tel: 01463 704663).
• Washout periods are required for switching between certain antidepressants (see below)
Antidepressant Swapping – General Guidelines
Fluoxetine, due to its long plasma half-life and active metabolite, may be stopped abruptly if the dose is 20mg/day.
When swapping from one antidepressant to another, abrupt withdrawal should usually be avoided. Cross tapering is preferred, where the dose of the ineffective or poorly tolerated drug is slowly reduced while the new drug is slowly introduced.
The speed of cross tapering is best judged by monitoring patient tolerability. No clear guidelines are available, so caution is required.
Note that the co-administration of some antidepressants is absolutely contra-indicated. See BNF Chapter 4.3.2 and Appendix 1. In other cases, theoretical risks or lack of experience preclude recommending cross tapering.
Withdrawal ideally involves a gradual reduction to a low dose of antidepressant before stopping.
Potential dangers of simultaneously administering two antidepressants include pharmacodynamic interactions (serotonin syndrome, hypotension and drowsiness) and pharmacokinetic interactions (e.g. elevation of tricyclic plasma levels by some SSRIs).
** Do not co-administer clomipramine and SSRIs or venlafaxine. Withdraw clomipramine before starting *1 Beware interactions with fluoxetine may still occur for five weeks after stopping fluoxetine because of long half-life.
Serotonin Syndrome – Symptoms
Death Duration of Treatment
Inadequate or no treatment for six months after the illness has resolved can result in relapse
rates as high as 50%.
Continue antidepressant drug treatment for a minimum of 6 months after remission of
symptoms in adults, and for a minimum of 12 months in the elderly.
Continue the same dose of antidepressant used that produced a response to treatment.
Patients with residual depressive symptoms and other factors increasing risk of relapse
should continue treatment for longer with the duration taking into account the persistence of
these factors. Maintenance Therapy
The risk of recurrence of depressive illness is high and increases with each episode.
Maintenance therapy should be at the same dose of antidepressant that produced a
response to treatment.
The decision to go on to maintenance therapy, rather than stop treatment at the end of the
continuation phase, must be made on clinical grounds in discussion with the patient.
Maintenance treatment with antidepressants is indicated for patients with:
• 3 or more episodes of depression in the last 5 years.
• Fewer recurrent depressive episodes but with persistent risk factors for
Re-evaluate patients on maintenance treatment, taking into account age, co morbid
conditions and other risk factors in the decision to continue the treatment beyond 2 years.
For the elderly, with two or more relapses, life long therapy is indicated. Discontinuation
Discontinuation symptoms can occur with all the major classes of antidepressant
Symptoms start abruptly within a few days of stopping the antidepressant
Symptoms usually resolve with days to 3 weeks
Risk factors: longer duration of treatment, short half life drugs such as paroxetine and venlafaxine If administered for 8 weeks or more, antidepressants should be reduced gradually over a minimum of 4 weeks. Fluoxetine may be an exception to this rule. Rapid discontinuation may be required for severe adverse reactions or if the patient switches into a manic state Ideally taper the dose over 6 months in patients who have been on longer-term maintenance treatment If discontinuation symptoms are mild then explanation and reassurance are often all that is required If severe symptoms are experienced consider the re-introduction of the original antidepressant (or another from the same class with a longer half life e.g. fluoxetine for paroxetine) and reduce gradually.
Discontinuation symptoms are varied and differ depending on the class of antidepressant.
Symptoms common to all classes include gastro-intestinal disturbance (nausea, abdominal
pain, diarrhoea), general somatic distress (sweating, lethargy, and headache), sleep
disturbance (insomnia, vivid dreams, nightmares) and affective symptoms (low mood,
anxiety, irritability). With the SNRI/SSRIs the commonest symptoms appear to be dizziness
and sensory abnormalities such as numbness or electric shock like sensations.
Discontinuation symptoms may be a useful clue to convert non-compliance. Antidepressants in pregnancy and breast-feeding
Updated advice in these areas can be obtained locally from the Area Medicines Information
Service (Tel. 01463 704288) or New Craigs Pharmacy Department (01463 704663).
Carefully consider the benefit/risk ratio of prescribing antidepressants during pregnancy and
breastfeeding for both mother and baby/foetus. Taking into account:
a. Antidepressants are not licensed for use in pregnancy & breastfeeding. b. There should be a clear indication for drug treatment c. Lowest effective dose should be given for the shortest period necessary d. Drugs with a better evidence base (generally more established drugs) are
Antidepressants in the first trimester
Evidence indicates no increased risk of major malformation or spontaneous abortion
following exposure to TCAs or SSRIs in early pregnancy. There is most evidence for
amitriptyline and imipramine in the TCA class, and most evidence for Fluoxetine in the SSRI
• Carefully assess the risks of stopping TCAs or SSRIs in relation to the
mother’s mental state & previous history
• There is no indication to stop TCAs or SSRIs as a matter of routine in early
• If a woman becomes depressed during pregnancy, antidepressants should be
prescribed with caution and specialist advice sought
Antidepressants after the first trimester
In later pregnancy there is evidence of neonatal toxicity and withdrawal at birth in infants
exposed to antidepressants. There are also concerns about the possible effects on infant
• Neonates exposed to antidepressants during pregnancy should be monitored
• Consider dose reduction and/or discontinuation 2 to 4 weeks before expected
delivery date then recommence after delivery.
Antidepressants during breast-feeding
Manufactures advise avoiding antidepressants during breast-feeding due to their excretion in
breastmilk and the evidence base is very limited. However there is no clinical indication for
women treated with TCAs (except doxepin) or the SSRIs paroxetine, sertraline or fluoxetine
to stop breast-feeding provided the infant is healthy and progress is monitored.
• Breast-feeding should take place immediately prior to taking medication,
ideally as a single daily dose just before the infant’s longest sleep period
• Ideally avoid breast feeding when maternal plasma levels are highest, usually
1 to 2 hours after taking the medication
• Paroxetine or Sertaline may be the preferred SSRIs.
A patient information leaflet concerning antidepressants and breastfeeding has been
produced by NHS Highland. This is written in plain English and is designed to assist the GP
in enabling the patient to come to an informed decision.
Antidepressants in cardiovascular disease
When initiating treatment in patient with ischaemic heart disease, sertraline is the treatment
ST JOHN’S WORT
When a patient has declined a number of offers of treatment for depression or expressed a
preference for St John’s Wort they should be informed that St John’s Wort may be of benefit
in mild and moderate depression. They should also be informed, as should those taking St
John’s Wort, of the interactions of St John’s Wort with other drugs, of the lack of information
on longer term efficacy and side effects and of the different strengths of the preparation
available and the uncertainty that arises from this
Always check if a patient is taking St John’s Wort if considering prescribing an
antidepressant. Suicide Screening Questions
When a diagnosis of Depression is made, suicide risk requires assessment. For all
depressed patients the following questions may be asked:
• Have these symptoms/feelings we've been talking about led you to think you might be
• This past week, have you had any thoughts that life is not worth living or that you'd be
• What about thoughts about hurting or even killing yourself? If YES
, what have you
Have you actually done anything to hurt yourself? Risk Factors
ASSESSMENT OF SUICIDE RISK
with patient to call you if suicide thoughts become more prominent; consult with an expert as needed.
Emergency assessment by qualified expert
Ind J Clin Biochem (Oct-Dec 2010) 25(4):367–370Effect of Metformin on Hormonal and Biochemical Profilein PCOS Before and After TherapyBratati Singh • Suchismita Panda • Rachita Nanda •Sanghamitra Pati • Manaswini Mangaraj •Pratima Kumari Sahu • Prakash Chandra MohapatraReceived: 18 September 2009 / Accepted: 24 September 2010 / Published online: 19 November 2010Ó Association of C
UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO Relación de la causa que se sigue en este Santo Oficio contra don Miguel Hidalgo y Costilla, cura de la congregación de los Dolores en el obispado de Michoacán, natural de (Testigo 1º denunciante fray Joaquín Huesca; folio 1º) .⎯ Tuvo principio esta causa por denuncia que fray Joaquín Huesca, mercedario, y lector de filosofía, hizo ante