Is described as follows: Heyrman J, Declercq T, Rogiers R, Pas L, Michels J, Goetinck M, Habraken H, De Meyere M. Recommendation for good medical practice: Depression in adults: approach by the general practitioner. Huisarts Nu 2008;37:284-317.
Patient input and consideration by the GP
Recommendations for good medical practice are guiding as support and guidance when making diagnostic or therapeutic decisions in general practice. They summarize for the general practitioner what is scientifically the best policy for the average patient. In addition, there is the agenda of the patient, who is an equal partner in decision-making. Therefore, the general practitioner clarifies the patient's question through appropriate communication and provides information about all aspects of the possible policy options. It is therefore possible that the general practitioner and patient together make a different best choice in a responsible and reasoned manner. For practical reasons, this starting point is not addressed repeatedly in the recommendations, but is explicitly stated here.
Introduction
Goal
This recommendation underpins the diagnostic and therapeutic approach to depression by general practitioners ( 1 ), aimed at adults and the elderly, including dysthymia, a chronic form with milder symptomatology, and recurrent depression.
This recommendation does not address depression in children and adolescents under 18 years of age ( 2 ), bipolar depression, psychotic depression and postpartum depression.
This recommendation specifically addresses general practitioners and their role in depression treatment ( 3 ). The contribution of the general practitioner is placed in the collaboration with other care providers involved. This recommendation takes into account the general working method of the general practitioner, consisting of rather short but frequent contacts that usually last no longer than twenty minutes.
This recommendation explicitly covers the entire area of depressive complaints that are presented to and treated by the general practitioner, both depressive complaints and the mild, moderate and severe forms of the depressive disorder ( 4 ). Almost all the scientific evidence is limited to the 'severe major' depressions, which occur less frequently in general practice than the milder forms ( 5 ).
Clinical questions
This recommendation answers the following clinical questions:
How does the GP diagnose depression?
What other elements besides the 'diagnosis of depression' should the GP assess in order to draw up a responsible care and therapy plan?
How does the GP draw up a customized care and therapy plan based on all the collected elements?
How does the GP structure the non-drug approach?
What is the place of antidepressant medication?
Which antidepressants does the GP prescribe? What is the starting and maintenance dose of the chosen antidepressant? How long should the antidepressant be given?
Which antidepressants does the GP prescribe for pregnant women, for breastfeeding women and for the elderly?
How does the GP organize the follow-up policy (medicinal and non-medicinal) and how does the GP conclude an episode of depression?
What aftercare does the GP provide to prevent relapse?
When, how and to whom can the GP – in a tiered care system – call upon external support?
What contribution does the GP make to prevent depression?
Epidemiology
One in five women and one in ten men experience depressive problems at least for a limited period in their lives. In Belgium, the prevalence of depression per year is 5 to 6% ( 6 ). Prevalences of depression recorded in general practitioner registrations are often much lower: 1 to 2% ( 7,8 ). It is unclear whether the difference between self-reporting of complaints and reporting of seeking help from a care provider is responsible for this.
Concepts, terms and definitions ( 9 )
The term depression in this recommendation refers to the broad range of mood disorders characterized as depressive, as presented to the general practitioner. In this recommendation, depression is considered a syndrome, as a disturbance of the mood with an intensity and/or duration that is no longer considered normal.
Three grades are distinguished according to severity and prognosis ( 10 ):
mild depression (minor, subliminal, subthreshold) ( 11 ),
moderate depression (mild to moderate major),
severe depression (severe major).
This provides a logical and clinically useful classification, with consequences for the initial therapeutic options and the expected prognosis.
By chronic depression we mean that the patient continues to show typical symptoms of depression for a period of at least two years. This also includes dysthymia, a chronic form with milder symptomatology ( 12 ).
The term recurrent depression is used from a second episode onwards ( 13 ). On average, 50% of patients with depression relapse and 25% have more than two episodes.
Pathophysiology of depression
Depression refers to a complex problem, of which multiple genetic, biological, psychological and social causes and influences are known. Recent literature integrates a multitude of research data, pathophysiological subconcepts and clinical messages in a so-called 'biopsychosocial depression model' ( 14,15 ).
Biopsychosocial depression model
The 'biopsychosocial depression model' characterizes a pronounced depression in an individual with the term 'derailed vulnerability'. A depressive mood disorder primarily indicates a long-standing vulnerability to depression. The fact that this manifests itself at a certain point is seen as the ultimate result of a negative spiral, set in motion by provoking factors that are no longer kept in balance by the positive protective factors that are present in every person to a greater or lesser extent. All these factors are situated on the biological, psychological and social level. Maintaining factors can perpetuate the condition.
There is a certain vulnerability to depression in every depressed patient. This vulnerability arises from the combination of a biogenetic predisposition and major life events ( 16 ). The vulnerable person can remain sufficiently upright for long periods or even his entire life and never show depression. The individual is said to owe this to protective factors ( 17 ).
Potentially provoking stressors test the resilience of the person and can be considered risk factors for depression ( 18,19 ). As an onset of the depressive episode, a negative spiral usually occurs at a certain point that installs the depression ( 20 ). Here, both negative thought processes and the loss of pleasure in previously enjoyable aspects of life play a reinforcing role. Interpersonal events, such as the loss of support figures and the reaction of the outside world, are also said to accelerate the negativity of this spiral.
Motivation for this guideline
General practitioners play a de facto central role in high-quality depression care; more than 80% of treated depressions are diagnosed and treated independently by the general practitioner. This finding certainly makes a specific recommendation for the contribution of general practitioners in depression treatment meaningful ( 21 ).
With this recommendation, the authors want to describe a broad depression model, adapted to the broad approach of the general practitioner. Specific attention is paid to the own diagnostic process that the general practitioner can follow. Furthermore, given the excessive attention for drug interventions, a specific step-by-step plan in the non-drug approach for the general practitioner is substantiated in this recommendation. Finally, the choice of a limited arsenal of antidepressants in the general practice is justified.
Several studies show that, under certain conditions, good guidelines can help to effectively treat depression in primary care ( 22 ). This refers to both including depression care itself, with or without support, and to taking over part of the aftercare and follow-up after referral.
Dealing with an episode of depression
When dealing with an episode of depression, we follow the GP's timeline:
First there is the process of diagnosis.
The diagnosis leads to a problem assessment that forms the basis for the care plan.
This care plan can be based on a drug and non-drug approach.
Once initiated, follow-up must be established until the episode is formally closed.
Then a more or less explicit aftercare starts, because relapses are frequent. This can lead to a status of chronic depression or dysthymia.
The GP's diagnosis
The GP follows a diagnostic process in four phases ( 23 ).
Be alert for possible depression
Within the broad range of daily complaints, often very vaguely and unclearly formulated, the GP must somehow become alert to the fact that 'this could well be a depression'. This 'alertness process' is difficult to standardize and is highly individual. The GP sometimes takes a long time to do it. It is described as rather 'empathetic' ('this pattern of complaints does have a number of depression characteristics') and 'normalizing' ('this can no longer be called normal for this patient or for these circumstances') ( 24 ).
The GP should be particularly alert to (non-exhaustive list):
vague, rather physical complaints such as sleep problems, fatigue, nausea, loss of appetite, weight loss, dizziness, (lower back) pain and other symptoms that can still lead in all kinds of diagnostic directions ( 25 );
a constantly changing presentation of the complaints during too frequent visits;
isolating behavior with abnormal inactivity, withdrawal, or avoidance features, especially in older isolated patients;
major life events such as major losses or disappointments such as divorce, loss of partner or child, loss of job;
serious somatic conditions such as acute myocardial infarction, malignant disease, stroke or other pathologies in the patient himself or his partner that are difficult to cope with because of their seriousness or loss of perspective in life;
history of depression, especially if there are also unexplained physical complaints, comorbidity with anxiety disorders, substance abuse or chronic pain.
Ask two, sometimes three, pointed questions to strengthen the suspicion ( 26,27 )
Question 1: During the past two weeks, have you often been bothered by feelings of depression or hopelessness?
Question 2: During the past two weeks, have you often been bothered by little interest or pleasure in the things you did?
Do not simply assume that the patient is asking for help for this. If in doubt, it may be appropriate to explicitly ask a third specific question, namely whether the patient would like help for this ( 28 ).
Systematic screening of all patients with more extensive and depression-standardized sets of questions is generally ( 29 ) and certainly not useful in general practice ( 30 ).
Rule out other possible explanations
Review the following four sets of questions to rule out other explanations for the complaints ( 31 ):
Question 1: Are there any serious and/or life-threatening treatable psychiatric conditions?
This includes:
Bipolar disorders: Has the patient ever had a manic or hypomanic episode or does this run in the family?
psychosis: is there evidence of hallucinations or delusions ( 32 )?
suicide risk: is there a serious risk of suicide? ( see further for estimating this risk )
If the answer to these questions is 'yes', an urgent referral to a specialized facility should be considered (psychiatrist, emergency facility, psychiatric department of a general hospital).
Question 2: Are there other treatable underlying problems that can present with depressive symptoms?
This includes somatic disorders:
hypothyroidism;
Parkinson's disease;
adverse drug effects: non-selective centrally acting beta-blockers (e.g. propranolol), benzodiazepines and other central nervous system depressants and centrally acting antihypertensives (e.g. methyldopa);
drug abuse: alcohol, cannabis, amphetamines, opioids.
Explore these somatic conditions and treat causally as much as possible.
Question 3: Are there treatable problems that are associated with depressive symptoms or depression, but rather require their own customized therapeutic approach?
Grief ( 33 ) at the death of an important person, whether unexpected or not, or other forms of loss in the circle of relationships or the work situation can cause depressive feelings. When they are no longer considered normal, one should be alert to depression.
Stress can be accompanied by a certain degree of depressive feelings. Stress is the clinical picture of tension complaints such as fatigue, irritability, insomnia that are related to an overloading situation and that result in temporary limitations in social or professional functioning ( 34 ).
The various anxiety disorders are sometimes accompanied by a certain form of depressive mood. Treat the anxiety. If depression is a significant part of the clinical picture, treat as depression.
Personality disorders can cause depression, but they can also affect the treatment and prognosis of depression.
Early dementia can present as depression or be accompanied by depressive feelings due to the realization of the loss, concentration problems and/or avoidance behavior ( 35 ).
Question 4: Are there any precipitating factors or known risk factors that could increase the suspicion of depression?
If there is any doubt about the diagnosis of depression, these essential components of the biopsychosocial basic concept can help to arrive at a diagnosis:
known vulnerability based on a family history of depression, known difficulties in the family and social environment during childhood, especially violence, maltreatment or sexual abuse or episodes of significant loss resulting in loss of self-esteem;
known difficulties in dealing with stress in the past;
elements of limited resilience such as a weak physical condition due to chronic illness or disability, unfavorable socio-economic factors or problems with psychological resilience, meaning and positive life goals.
Diagnose depression
In a number of patients, the diagnosis of a depressive disorder will now be clear to the GP thanks to the differential diagnostic process. This formally establishes the diagnosis of 'depression'. If there is any uncertainty, the following list of symptoms is used, as is customary in psychiatric diagnostics based on the DSM-IV-R ( see table ) ( 36 ). Please note that the symptomatology may be less pronounced in the elderly in particular and that all elderly people show a certain sense of loss ( 37 ).
Problem assessment of depression
Once the diagnosis of depression has been made, the prognosis is estimated. This largely determines the intensity of the care plan. Therefore, as a final diagnostic component, carefully assess the severity of the 'derailed vulnerability'.
The severity of the symptoms, including the impact on functioning, the perceived burden of suffering and the risk of suicide, provide information about the seriousness of the derailment.
The resilience is determined by the carrying capacity on a somatic level (physical condition), on a psychological level (defeatist, hurt, uncomprehending, helpless) and on a relational level (receives or does not receive support from family and other networks). This resilience is important for the chance of recovery from the negative depression spiral.
Provoking and protective factors not only determine the prognosis, they will also be important in designing the therapeutic intervention.
The care plan is drawn up on the basis of these elements.
Estimate the severity of the depression
Please note that this estimate is always a snapshot and can change!
Pay attention to the number of depression-related symptoms. This tells us something about the physical and psychological functions involved in the spiral of disturbance ( 38 ).
Pay attention to the intensity of each of these symptoms. Note that this is subjective, both on the part of the doctor and the patient. Some patients emphasize the symptoms, others minimize them.
Assess the impact on daily life. Five vital function areas are classically evaluated. Daily life is "greatly affected" by loss of interest in almost all activities, with inability to respond to pleasurable stimuli, marked reversal of circadian rhythm, with disinterest most severe in the morning and some relief in the evening, insomnia with early awakening, more than two hours earlier than usual, psychomotor retardation or agitation, and weight loss of more than 5% of body weight in one month.
Estimate the risk of suicide ( 39 )
Because patients often avoid talking about suicide, sensitivity to suicide signals ('suicide awareness') and active evaluation of the suicide risk by the GP are always necessary ( 40 ). This should also be repeated regularly during further follow-up.
Please note that suicidal ideation may also occur if the drug approach is effective in the first phase of treatment and the patient becomes more active again.
Be particularly alert for suicidal ideation in an elderly patient with depression, as epidemiologically the highest number of completed suicides is in the population over 70 years of age.
To assess your suicide risk, ask the following questions: Do you often feel hopeless? During those sad moments, do you ever think that life is no longer worth living or that life is no longer important to you, or that you would rather be dead? ( 41 )
If confirmed, explore further to what extent there is an active death wish: Do you ever think about ending your own life?
If the patient answers affirmatively, explore to what extent concrete plans exist: Are you thinking about how, where, when?
When making specific plans, ask about the availability of resources.
Check for a previous suicide attempt ( 42 ).
Be extra attentive if there is a certain calmness with which the patient speaks about this or if farewell letters have already been written or farewell rituals have already been planned. Then the suicide is only waiting to be realized.
Also ask about the frequency of the suicidal thoughts. Does this take on obsessive forms or is it only occasionally?
Ask if there has been a recent serious loss?
Is the patient single or does he or she have a good relational framework?
Is there severe pain or a recently diagnosed life-threatening illness?
Be alert if you have previously had problematic use of alcohol or drugs: relapse of alcohol abuse can cause inhibiting factors to disappear.
Questioning is useful because hopelessness is the single most important predictor of suicide.
Estimate the resilience
Ask how the patient has dealt with previous moments of stress and strain: How did you deal with these kinds of problems in the past, how did you manage to stay afloat at those moments?
Consider what you know about the patient in terms of how he dealt with difficult moments in the past.
In this way, try to gain insight into the patient's own problem-solving ability: How can I assess this person's strengths and weaknesses?
Check whether the person is in a supportive or negative network, as this will affect the chances of recovery.
Frame everything in the context of the whole person
Estimate the triggering factors. They tell something about the patient's sensitivity and tolerance to stress. Listen carefully to how the patient experiences this.
Determine whether the person had the cognitive and interpersonal skills in the past to process difficult moments and negative experiences.
Look at the comorbidity. Major disabling pathology plays a major role in the recovery process, as does the global fragility of, for example, the elderly, where a devastation in one area can lead to a devastation in many vulnerable areas.
Draw up the care and therapy plan now
Propose a therapy plan and intensity of care based on the assessment of severity, suicide risk, resilience and context.
We distinguish three degrees of depression based on severity, resilience and context ( 43 ).
Mild (minor, subliminal, subthreshold) depression ( 44 )
Severity grade: minor depression, with a rather mild mood disturbance or anhedonia, with complaints extending across two to four DSM-IV symptom areas, while the patient continues to function well overall.
Resilience assessment: in the past the patient has shown some resilience and/or is reasonably well embedded in a supportive network.
Contextual assessment: the patient still functions reasonably well in the various social systems and the disorder is primarily seen as a temporary reaction to disruptive factors. Very often, recognizable triggering factors will exist.
Recommendation ( 45 )
The GP remains vigilant and supports the patient's own resilience in a watchful waiting position. If necessary, elements from the non-medicinal approach (concretizing the complaint, psycho-education and activation) are added.
Moderate (mild to moderate major) depression
Severity grading: Symptoms are spread across five to seven symptom areas or less of greater intensity and impact, without actually causing a loss of vital functions.
Resilience assessment: prior to the depressive episode, the patient showed a period of reduced resilience or emotional vulnerability or is less embedded in a family or social network.
Contextual assessment: sometimes there are recognizable triggering causes, but sometimes not. Sometimes they are indicated, but they are disproportionate.
Recommendation ( 46.47 )
The GP proposes non-medicinal guidance as a first choice. He can do this in-house in the form of specifying the complaint, psycho-education and activation or he refers the patient for specialized psychotherapy.
In moderate depression, start medication if the patient:
refuses the non-drug approach,
explicitly requests medication,
has a history of major depression.
Severe (severe major) depression
Severity grade: a severe major depression with eight to nine symptoms of the DSM-IV list, of which at least the depressed mood and/or anhedonia, or fewer symptoms but with a great intensity and impact. Certainly if pronounced vital signs can be established or a pronounced suicide risk is present.
Resilience assessment: the patient's vulnerability is high and/or social support is low or even negative.
Contextual assessment: a burdened past, additional disabling pathology or global frailty.
Recommendation
The GP will suggest antidepressants and will initially suggest a referral to specialised psychotherapy ( 48 ). Cognitive behavioural therapy or interpersonal therapy is preferred ( 49 ). The consultation between the patient and the doctor is decisive in this ( 50 ).
The prognosis determination is therefore not a sum of parameters or a cumulative collection of facts. It remains an assessment by the clinician at the end of a diagnostic process, which may require adjustment at any later time. The prognosis assessment leads to a recommended approach. This takes into account the expectations and willingness of the patient and his or her environment. The approach is conditional and is evaluated on the achievement of the predetermined objectives. Adjustment may be necessary at any time depending on the changed assessment of the severity of the depression, the changing presence or absence of resources and supportive framework of the patient, the GP's own capabilities to handle depression, the degree and duration of the suffering, the patient's dysfunction, new signals for the risk of suicide and the positive response to the treatment instituted.
The GP's assessment and the recommended policy are discussed with the patient and tailored to his expectations. These expectations must be explicitly questioned. How does the patient view possible medication and non-medicinal interventions? Does the patient prefer to be treated by the GP or by other care providers? What exactly does he expect from these interventions?
Patient expectations are also not static, but evolve along with the process of diagnosis and treatment that the GP and patient go through.
Consultation requires a well-informed patient. With depression, difficulty making decisions can be one of the symptoms. With major depression with a great deal of suffering, poor contextual support and serious disruption of functioning, a more directive approach by the GP is sometimes more appropriate.
Non-medicinal care by the GP: a five-step plan
The general communication skills that a GP is expected to master are a necessary but insufficient condition for effective, non-medicinal treatment of depression. Depression counselling is in this sense a special form of psychosocial counselling, based on the basic principles of good conversation. Literature shows that the effectiveness of diagnostic identification, care assessment and counselling by GPs are influenced by:
the extent to which the physician dares to ask questions about affects and feelings ( 51 );
the communication skills of the physician ( 52 );
the physician's attitude towards depression ( 53 );
personal characteristics of the physician ( 54 );
patient's views ( 55 );
active follow-up strategies after diagnosis of therapy and adjustment of medication ( 56 ).
Three steps are essential for every GP ( 57,58 )
Step 1: Make the complaint and its impact on the patient's functioning concrete ( 59 )
Systematically explore the provoking and maintaining factors that are useful for framing the depression: recent changes in the patient's life and acute or chronic sources of stress.
Explore the ideas, concerns and expectations regarding the consultation and treatment (ICE) ( 60,61 ).
Make the complaint and how to deal with the complaint specific: Can we go over a time together when you felt very bad ( 62 )?
Give the patient space to respond to his mood complaints and relevant themes ( 63 ) from his life. If there are clear indications of traumatic experiences in the past, the doctor will, in consultation with the patient, save these for discussion ( 64 ) when the patient functions better in daily life again and the suffering of the symptoms has decreased.
Step 2: Psycho-education: naming and reframing the depression
Name the problem as 'depression'. If the patient has questions or resistance, listen to what objections he has to the diagnosis and give priority to those.
Provide adequate information about the condition 'depressive disorder' and a suitable explanation of the internal mechanism of what 'we medically call depression' ( 65 ). This includes the symptomatology of depression, its duration, course and impact. Provide information about the interaction between mind and body. Take into account the patient's thoughts about depression and correct if necessary. Provide the information in an atmosphere of consultation and regularly check against the patient's view.
Patients often look for a reason why they become ill. The biopsychosocial depression model can provide a place for the various elements that have played a role in the development or maintenance of the current depressive episode. Together, go over the influence of biopsychosocial vulnerability (stressors and maintenance factors) with attention to the carrying capacity ( 66,67 ).
Provide information on the therapeutic options (non-drug and drug ( 68 )) and their rationale ( 69 ).
Schedule a follow-up appointment promptly and state that regular follow-up is necessary for moderate or severe depression. For mild depression, mention the warning signs that would prompt the patient to contact the doctor again, especially if there was a history of depression. If the patient wishes, the doctor can recommend a number of books or websites with more information about depression ( 70 ).
Inform and support the partner of the depressed patient, if indicated.
Step 3: Activating the patient
Activate the patient through movement, sports ( 71 ) or by resuming activities that used to be pleasant, useful or valuable and/or gave a sense of competence ( 72 ). The patient's compliance with therapy depends on explaining how these activities have a beneficial effect on the course of a depression and on regularly monitoring progress in this. Choose the consultation model in terms of communication ( 73 ). Formulate small, feasible steps in activity. Use objectifying techniques such as keeping a diary or making a written report. In the case of severe apathy and total lack of energy and/or a psychotic depression, wait until the medication takes effect and in that case limit yourself to supportive conversations.
Discuss further with the patient:
the desirability of continuing to work or not,
the ability to fill in inactivity and create a concrete daily and weekly schedule,
the measures to promote sufficient sleep and normal sleep patterns ( 74 ).
Two more steps for the GP who wants to go a little further
General practitioners who have gained sufficient experience or who have specifically trained in psychotherapy can go two steps further or refer the patient to a psychotherapist ( 75,76 ).
Step 4: Working on the patient's cognitions ( 77 )
The biopsychosocial model of depression points to the importance and negative role that certain beliefs and thinking styles (such as black-and-white thinking) can play in the development and/or maintenance of the depressive mood.
The experienced GP discusses with the patient that the depression has an influence on the thinking, which maintains the depression. Training in learning to think differently can be proposed as an option for therapy. Then discuss the following points with the patient:
indicating the negative thoughts that have a provoking or maintaining effect on the course of the depression;
exploring depressing thoughts and thinking styles;
to see if the patient can view the environment, himself or the future differently. The doctor will adjust this and bring out the positive elements.
Step 5: Working on the underlying problem aspects ( 78 )
Discuss – if you have sufficient experience – actively what is fundamentally difficult in the patient's life and how he can solve this or learn to find a modus vivendi in it. This contributes to recovery. In all this, certainly give positive attention to the strong points of functioning and how the patient can strengthen them ( 79 ).
Focus the intervention on the meaning of the depression itself in this patient's life: Does this depression teach you anything about your way of life?
Focus the intervention on the triggers and how they can be interpreted differently: If this situation or reaction weighs so heavily on you, can we focus on that to possibly view it differently and learn to deal with it differently?
The GP with good system-oriented background can also acquire techniques that are useful for treating depression within the broader support system of the environment, the home front, the work situation, and friends.
The drug therapy of depression by the general practitioner
Due to the increasing evidence of publication bias, it is difficult in primary care to make a correct estimate of the expected effect of antidepressant medication in general and of SSRIs in particular. All recent publications show that the effect of this medication attributed to date has been overestimated and that the greatest effect of antidepressants can be expected in the group of patients with severe depression.
Positioning of the antidepressants
Only in the case of severe depression is antidepressant medication recommended as the first-line treatment 46. Initiate an antidepressant in the first consultation in the case of severe major depression with suicidality. In the case of mild or moderate depression, antidepressant medication is not the first choice in the first line ( 80 ).
Given the potentially serious adverse effects of all classes of antidepressants, starting an antidepressant should be a well-considered decision, taking into account the severity of the depression, the patient characteristics, the adverse effect profile of the chosen product, and the patient's wishes ( 81 ).
When starting an antidepressant, we recommend adding a specialized non-pharmacological approach in the form of cognitive behavioral therapy ( 82 ). In severe major depression, treatment consists of both pills and talking. It is a challenge for the GP to convince the patient that this combined approach consists of two equal interventions and that its success does not depend solely on adherence to the antidepressant medication.
First choice: TCA or SSRI?
Both a classic tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI) are defensible first-line drugs ( 83-85 ). No difference in effect has been demonstrated between the two groups of medication in outpatients. No differences in effectiveness have been demonstrated between the various TCAs and SSRIs in the general practitioner population ( 86,87 ). Once a decision has been made to prescribe an antidepressant, the risk of adverse effects of the chosen antidepressant and the risk of interactions with other medications are assessed for each individual patient.
As a general practitioner, we prefer to gain and maintain experience with a limited number of resources.
Choice of class
The GP uses five criteria to choose between the two classes of medication:
Adverse effects ( 88-90 )
The adverse effects in both classes of antidepressants differ not so much in severity, but rather in nature.
Prescribe an SSRI if the following adverse effects of TCAs would be a risk:
if anticholinergic effects such as dry mouth, constipation, blurred vision, urinary retention, sweating are undesirable;
in case of difficult micturition, untreated glaucoma;
if cardiac side effects such as arrhythmia and orthostatic hypotension (with dizziness) are feared;
TCAs are an absolute contraindication after a recent myocardial infarction, in heart failure or in cardiac arrhythmias.
Prescribe a TCA if the following adverse effects of SSRIs would be a risk:
gastrointestinal adverse effects such as nausea, anorexia and diarrhea;
central nervous system adverse effects such as dizziness, agitation, insomnia and tremor;
fatigue;
extrapyramidal symptoms (mainly seen with paroxetine);
increased risk of upper gastrointestinal bleeding ( 91 );
electrolyte disturbances in the form of hyponatremia (especially in the elderly) ( 92 ).
Sexual adverse effects are seen with both classes of antidepressants and should be explicitly inquired about, as they may be a reason for premature discontinuation of antidepressant treatment ( 93 ).
A recent review found that the use of some antidepressants increases the risk of aggressive behavior in a limited subgroup of patients ( 94 ).
Most adverse effects are generally considered to be transient (patients develop tolerance with continued use). However, some adverse effects are serious, persistent and may lead to premature discontinuation of medication.
Interactions
If the patient is already taking other serotonergic drugs such as dextromethorphan or triptans, the GP will preferentially prescribe TCAs ( 95 ). The combination of an NSAID with an SSRI further increases the risk of serious gastrointestinal bleeding. The combination of diuretics and SSRIs gives an increased risk of hyponatremia. The combination of an SSRI with an antipsychotic gives an increased risk of extrapyramidal side effects. Finally, some SSRIs interact with other drugs via metabolism by the same cytochrome P450 isoenzyme. Citalopram, escitalopram and sertraline do not significantly inhibit these CYP isoenzymes ( 96 ). Therefore, in elderly patients, the GP will choose an SSRI that shows a minimum of interactions, namely sertraline or citalopram ( 97 ).
The half-life of the chosen medication ( 98 )
Fluoxetine has a very long half-life (three to four days for the molecule itself, seven to fifteen days for the active metabolite), partly due to the presence of an active metabolite, and is therefore best avoided in the elderly.
The toxicity of the chosen product and the risk of suicide ( 99 )
In themselves, TCAs are more toxic in overdose than SSRIs and there is therefore a greater chance of a completed suicide with an overdose of TCAs than with SSRIs. In severe major depression with active suicidality, an SSRI is therefore chosen by consensus over a TCA.
Both TCAs and SSRIs can increase or induce suicidal thoughts or suicide in adults during the first phase of treatment. The GP will monitor the patient closely (at least weekly) at the start of treatment with antidepressants in order to recognize the risk of suicide in time.
The cost price
TCAs are cheaper than SSRIs.
The choice of antidepressant and its practical use
When is it decided to prescribe a TCA?
Preference is given to amitriptyline (sedative), imipramine (neutral) or nortriptyline (activating) because the most experience has been gained with these agents. The nature of the depression (for example severe depression with insomnia or agitation) determines the choice of product (amitriptyline in this example) ( 100 ). Clomipramine is the first choice if the depression is also accompanied by anxiety. In the elderly patient, preference is given to nortriptyline because of the small number of anticholinergic side effects of this molecule.
TCAs are started in a escalating dose: for example, start a (young) adult patient with amitriptyline 25 mg before going to bed. This dose is increased by 25 mg every two to three days, up to 100 mg before going to bed. The average maintenance dose is 100 mg before going to bed; such a (low) dose has also been shown to be effective in the first line ( 101 ). A dose lower than 75 mg is assumed to be ineffective in the (young) adult patient. In the older patient, start with nortriptyline 10 to 25 mg in the morning. This dose can be increased by 25 mg daily to a maximum daily dose of 50 mg. The maintenance dose in the older patient is therefore significantly lower than in the (young) adult patient and is assumed to be effective here.
When is it decided to prescribe an SSRI
All SSRIs are in principle equal. The GP chooses between fluvoxamine (more sedative), paroxetine, fluoxetine (activating), sertraline or citalopram. Preferably do not use escitalopram because this enantiomer is much more expensive than the parent molecule citalopram and there is as yet no proven added value of this product in primary care compared to other SSRIs ( 102 ). Fluvoxamine is said to have more undesirable effects than fluoxetine, sertraline and paroxetine ( 103 ). Preferably use citalopram and sertraline in the elderly because of their minimal chance of interaction with other medicines. In this age group, it is best not to use fluoxetine because of the very long half-life of this product and its active metabolite.
The dosage of fluoxetine is 20 mg in the morning, of fluvoxamine 100 mg in the evening, of paroxetine 20 mg in the morning, of sertraline 50 mg in the morning or evening and of citalopram 20 mg in the morning. Start with this dosage immediately; a gradual increase is usually not necessary. In the elderly patient, a reduced dose will be started (for example half the usual dose) and increased to the normal daily dose.
Explanation to the patient
Explain to the patient that the effect on mood will not be noticeable until after two to four weeks and that any unwanted effects will precede the intended desired effect.
Consider the small but real possibility of increased suicidal ideation when initiating antidepressant medication.
Some adverse effects (such as sedation) usually diminish gradually or the patient becomes accustomed to them ( 104 ). Other adverse effects (such as dry mouth) may be persistent or severe, resulting in discontinuation of therapy.
Warn about the possible negative effect on driving ability during the first month of taking the antidepressant and when increasing the dose or when using other psychotropic substances such as alcohol at the same time.
Finally, inform your patient about the risk of withdrawal symptoms if his antidepressant treatment is suddenly stopped.
Depression with severe agitation, anxiety or insomnia
In severe depression, it is advisable to adapt the choice of antidepressant to the specific nature of the depression, which usually means that there is no need for a benzodiazepine as auxiliary medication. If the GP nevertheless opts in exceptional cases, for example due to severe restlessness or anxiety, to start a short-term (pending the effectiveness of the antidepressant) low dose of lormetazepam (for severe insomnia) or diazepam (for severe anxiety), this benzodiazepine should be reduced after four weeks ( 105 ).
Other possible antidepressants
The other non-tricyclic antidepressants, namely moclobemide, mianserin, maprotiline, reboxetine and mirtazapine and the non-specific serotonin reuptake inhibitors, venlafaxine and trazodone are not first-line drugs. They have not yet proven to be of sufficient added value or show a potentially more serious side effect profile ( 106 ).
As for the serotonin and norepinephrine reuptake inhibitor (SNRI) duloxetine, we still have too little data to make a substantiated statement ( 107 ).
Hypericum perforatum is also not recommended ( 108 ).
Antidepressants during pregnancy and breastfeeding ( 109,110 )
A non-pharmacological approach is preferred, but continuing or initiating antidepressant treatment may be warranted in some cases.
Consider the risk of relapse of depression when deciding to discontinue antidepressants in a woman who is pregnant or who may become pregnant.
In patients who are already taking an antidepressant and become pregnant, it is best to discuss with the psychiatrist and obstetrician to what extent continuing treatment is indicated.
Seek psychiatric advice and advice from the obstetrician if a pregnant woman develops a serious depression requiring an antidepressant.
Provide a minimum effective dose during pregnancy because of the risk of perinatal problems in the newborn and the possibility of impaired psychomotor development after exposure to psychotropic medication.
Reduce the dose or stop the antidepressant two to four weeks before delivery and restart after delivery.
Neonates exposed to psychomotor drugs during pregnancy should be closely monitored for several days after delivery.
In breast-feeding, a TCA can be given if the child is healthy and its evolution is being monitored. Imipramine is preferred. Of all the SSRIs, paroxetine has the lowest serum concentrations in the breast-fed child. Whenever possible, the antidepressant should be administered in a single dose for the longest period of sleep in the child. Breast-feeding is best continued immediately prior to administration of the medication and avoided for one to three hours after administration.
Antidepressants in the elderly patient ( 111-115 )
Prescribe antidepressants for severe depression in the elderly.
Carefully weigh the expected benefits and harms of the antidepressant, as comorbidity and polypharmacy are common.
Monitor closely for any adverse effects that may occur.
Do not deny an elderly person with severe depression an antidepressant because of the increased risk of morbidity and mortality from depression in this age group ( 116 ).
When an antidepressant is started in an elderly patient, a non-drug approach will always be added, if possible by a multidisciplinary team that includes informal care, home care (including nurses and carers), physiotherapist, general practitioner and psychiatrist ( 117 ).
Preferred product for the elderly patient
Prescribe an SSRI rather than a TCA ( 118 ). Citalopram and sertraline are acceptable choices because of their low risk of drug interactions. Fluoxetine is discouraged because of its very long half-life. Fluvoxamine is reported to have more adverse effects than fluoxetine, paroxetine, and sertraline ( 119 ).
In a patient with gastrointestinal risk, for example (bleeding) gastric ulcer in the past, Parkinson's disease and concomitant use of NSAIDs (including acetylsalicylic acid), nortriptyline is the preferred product ( 120 ).
Initiating an antidepressant in the elderly patient
For an SSRI, use the 'start low, go slow' principle: the dosage is increased more slowly in the elderly than in the adult non-elderly patient. The starting dose of citalopram or sertraline, for example, is half the usual dose and can be slowly increased to the normal dose for (young) adult patients, which is one tablet daily.
When initiating an SSRI, pay particular attention to possible interactions with other medications. Consider the increased risk of hyponatremia in this population and the possibility of gastrointestinal bleeding.
The 'start low, go slow' principle is also used when starting TCAs. For nortriptyline, start with 10 to 25 mg per day and slowly titrate up to a maintenance dose of maximum 50 mg daily.
Follow-up policy by the GP
The GP will take the initiative to schedule follow-up interviews with the patient. At the start, weekly interviews are usually recommended; if the evolution is favourable, biweekly to monthly interviews may suffice ( 121 ). In the case of threatened suicide and if no admission has been made, much stricter follow-up, for example every few hours to daily, is necessary.
Depressive episode
Non-drug approach
Ensure that follow-up addresses both residual complaints and signs of recovery; actively ask the patient what he or she has done to achieve this progress.
Tell the patient that the course is a process of 'trial and error'. If not, a gloomy day after a few better days can quickly be seen as a relapse or as evidence that no improvement is possible, so that demoralization threatens. It is important that the patient gets the feeling that after an improved mood, a relapse in mood is part of the normal evolution.
Take the opportunity – when the negative experience and assessment gradually diminish and the patient starts to function 'normally' again – to place the depression in a broader context of meaning: themes from the former life and the vulnerabilities can now be discussed. In doing so, particular attention should be paid to the way in which the patient can learn to deal with his vulnerability differently. The further development of the patient's strong points is also a point of attention.
Opt for less intensive guidance if the positive evolution continues ( 122 ).
If the response to the non-drug approach is insufficient, an antidepressant is added.
Drug approach
Close follow-up, at least weekly during the first weeks of taking an antidepressant, is recommended because of the increased risk of suicidal ideation during the early treatment of major depression.
Evaluate the effect of the medication after four weeks (adult patients) to six weeks (elderly patients).
In case of partial or insufficient response within these periods, it is advised to continue treatment for another two weeks (adults) to six weeks (elderly) until there is sufficient response, provided that the side effects are acceptable ( 123,124 ). A re-evaluation of the diagnosis may need to be considered and the GP may refer to a psychiatrist.
If there is still no (sufficient) response after these additional weeks, we speak of treatment-resistant depression. It is unclear whether increasing the dose can also lead to an increased chance of effectiveness of the antidepressant started.
If there is a sufficient response and no or acceptable adverse effects (after four or six weeks in adults; six or twelve weeks in the elderly), the medication is continued until complete remission. After remission, treatment is continued for another six months for the treatment of a first episode of major depression ( 125 ). In patients with residual complaints after the six months, in patients with a history of depression and in the elderly, a longer period of treatment is indicated, for example nine to twelve months instead of six months.
In case of unacceptable side effects, the medication is reduced and another antidepressant is started in consultation with the patient. It is then advisable to choose a drug from another group ( 126 ).
In case of treatment-resistant depression or an acute phase non-responder (from the patient's point of view) - this is no response to a first antidepressant given for a sufficient period of time and in an adequate dose - the diagnosis should be reconsidered and the GP will refer to the psychiatrist and/or involve an outpatient home care team ( 127 ).
Closing the treatment
Ending non-drug guidance ( 128 )
An important moment is the formal conclusion between GP and patient of the current depression episode. At that moment an evaluation is useful: what the patient experienced as help and how in the future attention can continue to be paid to possible relapse, preferably at an early stage (environment can be involved as co-monitor).
Ending drug therapy ( 129 )
If medication has been started, it will be reduced before the non-medicinal support is stopped. After a treatment of, for example, six (adults) or nine to twelve (elderly) months, the medication is gradually reduced over a period of at least four weeks to avoid withdrawal symptoms ( 130 ). In concrete terms, this means that, for example, approximately two fewer daily doses are given per week.
Aftercare, relapse prevention and the transition to chronic depression
Aftercare for depression
Given the risk of relapse for some depression patients, agreements should be made about a possible relapse. Discussing this in advance has the advantage that the patient does not necessarily see a relapse as failure.
Important points of attention are:
always being on the lookout for alarming signals;
the 'demining' of bad days or moments as a predictor of relapse ( 131 );
promoting and maintaining health behaviors;
continue to monitor how the patient deals with previously stress-provoking factors and pay attention to his protective factors;
encouraging the resumption of previously useful strategies in dealing with complaints when signs of relapse appear.
Recurrence of depression
About half of patients will have a second depressive episode at some point, and another half will have a third episode. For some patients, it even becomes a recurring condition, a chronic depression.
In case of a recurrence, the GP will re-evaluate the diagnostic assessment and the treatment options. The option may be to restart the guidance process together with the patient. In the context of the 'stepped-care' approach, a recurrence can also be a signal to opt for a more intensive guidance scheme, with the involvement of more or more specialized help.
Relapse prevention
Drug prevention of relapse
Prevent relapse by treating at-risk patients with antidepressants for a longer period after remission, for example nine to twelve months instead of the usual period of six months. After this longer period, it is recommended to reduce medication over a period of at least three months.
Discuss each case separately with the psychiatrist if longer-term treatment, for example treatment lasting several years, is required ( 132 ).
Non-drug prevention of relapse
Consider the decreasing degree of effectiveness in relapse of behavioral therapy, competence-enhancing techniques, psycho-educational techniques and multiple approaches in one approach, if it is decided to refer the patient with a relapse. Cognitive techniques and increasing social support do not show a significant additional effect compared to the other programs for preventing relapse. Cognitive therapy would have a clear additional effect on top of antidepressants, especially if residual symptoms are still present ( 133 ).
If necessary, organize a more active follow-up strategy, in which an increase in compliance with medication or additional therapy can be expected ( 134 ).
New approaches are being developed, especially to set up even more intensive therapy schemes in cases of frequent relapses. Some, including mindfulness-based cognitive therapy, have already built up a certain evidence base ( 135 ).
When Depression Becomes Chronic: Chronic Depression and Dysthymia
Patients can still show certain typical depression symptoms for longer periods after relative or partial recovery. If this lasts for more than two years, we speak of chronic depression.
Dysthymia is a specifically described mild form of chronic persistent depression in which the depressed mood is present for most of the day, more days than not, for at least 2 years ( 136 ). The prevalence of dysthymia increases with age ( 137 ).
In accordance with the guidelines in the NHG Standard, we propose to also treat patients with dysthymia primarily non-medicinal. If this non-medicinal approach is not effective enough, a trial treatment with antidepressants can be considered ( 138 ).
Graduated care and collaboration
There is evidence that collaboration improves the quality of care for depressed patients, is cost-effective and has a beneficial effect in preventing relapse ( 139,140 ).
We advocate the use of a wide range of forms of cooperation, including the classic referral, in a customized manner. In the context of drawing up a care plan for each depressed patient, this variety of care is gradually activated based on the assessment of the severity of the depression, the risk of suicide, the resilience and the context. The patient's preference, the possibilities of the GP and the local facilities also play a role in the choice of the content of the care plan ( 141 ).
Support self-care
In case of any depression, support the patient's self-care by, for example, using self-help books or by joining self-help groups or other regional initiatives.
Enable informal care
In every depression, involve the informal caregiver as much as possible to gain insight into the patient's relationships. These relationships can play a role in the development of the depression and during the recovery process. Inform the relevant people in the patient's environment about his depression - if he agrees - and actively involve them in the recovery process.
Home care
Ask for advice on strengthening home care from a psychiatrist, a Mental Health Center (CGGZ), a self-employed psychologist, a General Welfare Center (CAW) or another welfare organization ( 142 ). There are three reasons for seeking advice ( 143 ):
In connection with the diagnosis: ask a psychiatrist for advice if comorbidity is suspected (anxiety disorders, personality disorders) or in case of substance abuse. Ask for advice about the diagnosis in case of treatment-resistant depression or if there is insufficient response to the prescribed antidepressant in case of severe depression. Sometimes advice will not be sufficient and referral is necessary.
In connection with the drug approach: ask a psychiatrist for advice about the medication in case of a treatment-resistant depression, in case of a recurrent depression, in case of a serious depression during pregnancy. Also if a relapse requires years of drug treatment, we recommend a consultation with the psychiatrist for each case separately.
In connection with psychosocial support: ask for advice from the CGGZ, CAW, OCMW, health insurance fund or home care services in case of social isolation, limited financial capacity, employment problems and the like ( 144 ).