Diagnosis and Treatment of Depression in Patients With MS
Diagnosis and Treatment of Depression in Patients With MS
There is no simple and perfect way to screen for depression. Most scales are not specific for MS, except for the recently reported MS Depression Rating Scale. Among the most used scales are the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Both are relatively simple and can be used by clinicians during routine consultations, but they may not be as simple for the patient. BDI and HADS use gradations of given symptoms, ranging from practically never to always, with some options between these extremes. Having BDI and HADS as the screening scales may discourage clinicians from routinely looking for depression. Therefore, Spitzer et al's two questions for depressed mood and anhedonia provides a simpler approach:
This two-question instrument was 96% sensitive with a negative likehood ratio (LR) of 0.07 and a negative predictive value of 98%. This simple method correctly identified 99% of depressed patients with MS.
Of course, the two questions do not replace BDI and/or HADS and do not come close to a full neuropsychological evaluation. However, including these two questions as routine in every MS consultation may alert neurologists to cases requiring more extensive evaluation.
Clinicians should ask all MS patients the two questions on depressive mood and anhedonia. If the answer is 'no' to both, the probability of depression is less than 2%. If the answer is 'yes' to both, the probability of depression is 99%.
Anxiety: About half the number of patients with MS report anxiety Depression, female sex, low levels of self-efficacy, disability and stress increase its prevalence, but only depression is an independent predictor. The literature suggests that anxiety clearly associates with reduced health-related quality of life, unrelated to neurological disability.
Obsessive compulsive disorder may affect as many as 16% of patients with MS. It is associated with bipolarity, depression and anxiety in the general population, but these associations have not yet been studied in patients with MS.
Other psychiatric conditions that are also more frequent in MS than in controls include sleep impairment, somatisation, interpersonal sensitivity, anger–hostility, phobic anxiety, paranoid ideation, psychoticism, low self-esteem and distorted eating attitudes.
Clinicians should be aware that patients with MS have greater risk of anxiety, bipolarity and obsessive-compulsive behaviour. Patients with MS who already have depression may also develop other less common, but equally distressing psychiatric symptoms.
Patients with MS have a considerably increased risk of suicide, relating to depression, and not to disability. Risk factors include depression, social isolation, lower income and younger age, as well as male sex, disability, a sense of hopelessness and loss of control. Effective treatment of depression reduces suicide risk; unfortunately, most cases of severe depression and suicide ideation in MS remain undiagnosed and untreated.
Clinicians should be alert to the risk of suicide in patients with MS. In patients with moderate to severe depression, suicide ideation must be assessed.
Lower quality of life with MS appears more a function of depression than of chronic disability. Disability itself does not seem to lead specifically to depression. While disability from an acute relapse may cause depression, it often persists after recovery from the disability. Depressed patients complain more about their disability-related executive impairment than do non-depressed patients.
Clinicians should suspect depression in MS patients who report a degree of disability out of keeping with their physical signs.
Fatigue is defined as physical and/or mental weariness resulting from exertion, lack of energy or tiredness. It is common in central and peripheral neurological disorders. Fatigue in MS is perhaps the single most debilitating symptom, surpassing pain and even physical disability. Fatigue significantly impairs quality of life in MS.
Half of all patients with MS report depression at some period of their lives, and fatigue affects at least 75%, persisting over time; thus, many patients with MS have both. Tiredness and lack of energy—typical of depression and fatigue—correlate with sleep disturbances. A recent imaging study showed a pattern of diffuse grey matter atrophy that related to fatigue and depression in patients with MS.
The presence of fatigue in MS should alert clinicians to the possibility of depression.
There is no standard method to assess cognition in patients with MS: over 30 tests are currently used. Depressed mood in MS may worsen cognition, and particularly attention and interest. Although some studies show no specific correlation between depression and cognitive dysfunction in MS, depression probably does affect cognitive performance. In fact, fatigue and depression are the main correlates of cognitive impairment in MS. Thus, depression may exaggerate the features of cognitive disability while not necessarily worsening performance. Unemployment and poor social life, sometimes (but not always) relate to physical disabilities, and may also negatively influence cognition leading to further isolation and frustration.
Depression may influence cognitive performance, but also influences a patient's interpretation of his/her cognitive dysfunction. Patients whose 'memory' complaints are prominent and apparently unrelated to their cognitive state, require screening for depression.
Patients with MS and depression are twice as likely not to adhere to disease-modifying drug treatment, particularly if they have not taken antidepressants for at least 6 months. In a large study in the King county (USA) population of patients with MS, 19% had excessive alcohol consumption, overuse of prescribed medications and illicit substance abuse, and particularly those with depression. Although there are no specific studies in MS, patients who consume alcohol are less likely to adhere to treatment because they are concerned that the combination may be toxic.
In a patient with MS and depression, clinicians should assess adherence to treatment at every consultation. Alcohol and drug consumption must also be addressed, since these habits may influence adherence.
Disease-modifying drugs may induce or exacerbate depression, improve depression and not alter depression. This aspect of MS treatment needs investigation through long-term pharmacovigilance. There are only anecdotal reports and small case series, and no substantial conclusions.
Interferon β: The leaflets accompanying interferon β 1a (subcutaneous and intramuscular) and 1b (subcutaneous) include warnings about their use in depression and/or previous psychiatric history. However, this is controversial. There are reports of severe depression and suicide attempts among MS patients treated with interferon β who had no prior psychiatric history. On the other hand, others have found no evidence to support interferon-β alone causing or exacerbating depression. Nonetheless, because of the apparently higher risk of depression in patients with MS treated with interferon β, this treatment requires screening for signs of depression and, if necessary, appropriate antidepressant treatment.
Glatiramer acetate: The leaflet accompanying this medication specifies depression as an adverse effect. There are no data on the prevalence, characteristics or risk factors for depression in patients using glatiramer acetate. There is a hypothesised but unproven theory of potential antidepressant effects from glatiramer acetate. Overall, the risk of depression from glatiramer acetate apears no higher than with interferon-β, and in both the risk is small. However, as with interferon-β, it is sensible to screen patients who receive glatiramer acetate or signs of depression, and treat them appropriately if necessary.
Natalizumab: A retrospective analysis on the depression data of the phase III SENTINEL study on natalizumab showed that a significant number of patients who entered the trial without depression developed a positive score for depression during the trial. On the other hand, a more recent phase IV study analysing fatigue in patients treated with natalizumab showed better scores for depression among treated patients. The leaflet accompanying the drug warns of depression as a potential adverse effect.
Fingolimod: Fewer than 5% of patients using fingolimod develop depression, and depression is not among the 15 most common listed side effects of the drug. Studies analysing fingolimod's adverse events found no significant differences in development or worsening of depression However, the leaflet accompanying the drug lists depression as a potential adverse effect of the drug.
Patients with MS must be screened for depression before and during treatment with disease-modifying drugs.
Pharmacological treatment: Despite the high prevalence of depression in patients with MS and the potential danger of suicide, there are remarkably few methodologically sound papers on the subject. A Cochrane review identified only two studies, one using paroxetine and the other using desipramine. Each included only small patient numbers and short-term treatment. Adverse events were frequent, while several patients dropped out or were lost to follow-up. It is difficult to draw definite conclusions from these studies, but both drugs showed only a trend toward improving depression in MS. The confidence intervals were wide and there were no statistically significant differences between any of the drugs and placebo for any of the outcomes.
There have been open trials treating depression in MS using sertraline, moclobemide and fluoxetine, and duloxetine. Again, these were isolated studies with small numbers of patients and relatively short follow-up. The tendency to use selective serotonin receptor reuptake inhibitor is justified since tricyclic antidepressants could induce somnolence, reduce cognitive performance and exacerbate fatigue.
Non-pharmacological treatment: Individual cognitive-behavioural therapy, group psychotherapy, or sertraline were compared in an open trial on depressive patients with MS. There were no significant differences between these treatments, although the samples were small and the drop-out rate was around 20%. At least over the short term, individual cognitive behavioural therapy seems a good non-pharmacological alternative to treat depression in MS.
There are no evidence-based guidelines to treat patients with MS who present with depression; the choice depends upon the efficacy and tolerability of the drugs used to treat depression generally.
Simple Methods for Screening for Depression
There is no simple and perfect way to screen for depression. Most scales are not specific for MS, except for the recently reported MS Depression Rating Scale. Among the most used scales are the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Both are relatively simple and can be used by clinicians during routine consultations, but they may not be as simple for the patient. BDI and HADS use gradations of given symptoms, ranging from practically never to always, with some options between these extremes. Having BDI and HADS as the screening scales may discourage clinicians from routinely looking for depression. Therefore, Spitzer et al's two questions for depressed mood and anhedonia provides a simpler approach:
During the past month, have you often been bothered by feeling down, depressed, or hopeless?
During the past month, have you often been bothered by little interest or pleasure in doing things?
This two-question instrument was 96% sensitive with a negative likehood ratio (LR) of 0.07 and a negative predictive value of 98%. This simple method correctly identified 99% of depressed patients with MS.
Of course, the two questions do not replace BDI and/or HADS and do not come close to a full neuropsychological evaluation. However, including these two questions as routine in every MS consultation may alert neurologists to cases requiring more extensive evaluation.
Clinicians should ask all MS patients the two questions on depressive mood and anhedonia. If the answer is 'no' to both, the probability of depression is less than 2%. If the answer is 'yes' to both, the probability of depression is 99%.
Concomitant Psychiatric Conditions
Anxiety: About half the number of patients with MS report anxiety Depression, female sex, low levels of self-efficacy, disability and stress increase its prevalence, but only depression is an independent predictor. The literature suggests that anxiety clearly associates with reduced health-related quality of life, unrelated to neurological disability.
Obsessive compulsive disorder may affect as many as 16% of patients with MS. It is associated with bipolarity, depression and anxiety in the general population, but these associations have not yet been studied in patients with MS.
Other psychiatric conditions that are also more frequent in MS than in controls include sleep impairment, somatisation, interpersonal sensitivity, anger–hostility, phobic anxiety, paranoid ideation, psychoticism, low self-esteem and distorted eating attitudes.
Clinicians should be aware that patients with MS have greater risk of anxiety, bipolarity and obsessive-compulsive behaviour. Patients with MS who already have depression may also develop other less common, but equally distressing psychiatric symptoms.
Suicide Risk
Patients with MS have a considerably increased risk of suicide, relating to depression, and not to disability. Risk factors include depression, social isolation, lower income and younger age, as well as male sex, disability, a sense of hopelessness and loss of control. Effective treatment of depression reduces suicide risk; unfortunately, most cases of severe depression and suicide ideation in MS remain undiagnosed and untreated.
Clinicians should be alert to the risk of suicide in patients with MS. In patients with moderate to severe depression, suicide ideation must be assessed.
Disability and Depression
Lower quality of life with MS appears more a function of depression than of chronic disability. Disability itself does not seem to lead specifically to depression. While disability from an acute relapse may cause depression, it often persists after recovery from the disability. Depressed patients complain more about their disability-related executive impairment than do non-depressed patients.
Clinicians should suspect depression in MS patients who report a degree of disability out of keeping with their physical signs.
Fatigue and Depression in MS
Fatigue is defined as physical and/or mental weariness resulting from exertion, lack of energy or tiredness. It is common in central and peripheral neurological disorders. Fatigue in MS is perhaps the single most debilitating symptom, surpassing pain and even physical disability. Fatigue significantly impairs quality of life in MS.
Half of all patients with MS report depression at some period of their lives, and fatigue affects at least 75%, persisting over time; thus, many patients with MS have both. Tiredness and lack of energy—typical of depression and fatigue—correlate with sleep disturbances. A recent imaging study showed a pattern of diffuse grey matter atrophy that related to fatigue and depression in patients with MS.
The presence of fatigue in MS should alert clinicians to the possibility of depression.
Cognitive Dysfunction and Depression in MS
There is no standard method to assess cognition in patients with MS: over 30 tests are currently used. Depressed mood in MS may worsen cognition, and particularly attention and interest. Although some studies show no specific correlation between depression and cognitive dysfunction in MS, depression probably does affect cognitive performance. In fact, fatigue and depression are the main correlates of cognitive impairment in MS. Thus, depression may exaggerate the features of cognitive disability while not necessarily worsening performance. Unemployment and poor social life, sometimes (but not always) relate to physical disabilities, and may also negatively influence cognition leading to further isolation and frustration.
Depression may influence cognitive performance, but also influences a patient's interpretation of his/her cognitive dysfunction. Patients whose 'memory' complaints are prominent and apparently unrelated to their cognitive state, require screening for depression.
Adherence to Treatment
Patients with MS and depression are twice as likely not to adhere to disease-modifying drug treatment, particularly if they have not taken antidepressants for at least 6 months. In a large study in the King county (USA) population of patients with MS, 19% had excessive alcohol consumption, overuse of prescribed medications and illicit substance abuse, and particularly those with depression. Although there are no specific studies in MS, patients who consume alcohol are less likely to adhere to treatment because they are concerned that the combination may be toxic.
In a patient with MS and depression, clinicians should assess adherence to treatment at every consultation. Alcohol and drug consumption must also be addressed, since these habits may influence adherence.
Disease-modifying Drugs (Interferon-β, Glatiramer Acetate, Natalizumab, Fingolimod)
Disease-modifying drugs may induce or exacerbate depression, improve depression and not alter depression. This aspect of MS treatment needs investigation through long-term pharmacovigilance. There are only anecdotal reports and small case series, and no substantial conclusions.
Interferon β: The leaflets accompanying interferon β 1a (subcutaneous and intramuscular) and 1b (subcutaneous) include warnings about their use in depression and/or previous psychiatric history. However, this is controversial. There are reports of severe depression and suicide attempts among MS patients treated with interferon β who had no prior psychiatric history. On the other hand, others have found no evidence to support interferon-β alone causing or exacerbating depression. Nonetheless, because of the apparently higher risk of depression in patients with MS treated with interferon β, this treatment requires screening for signs of depression and, if necessary, appropriate antidepressant treatment.
Glatiramer acetate: The leaflet accompanying this medication specifies depression as an adverse effect. There are no data on the prevalence, characteristics or risk factors for depression in patients using glatiramer acetate. There is a hypothesised but unproven theory of potential antidepressant effects from glatiramer acetate. Overall, the risk of depression from glatiramer acetate apears no higher than with interferon-β, and in both the risk is small. However, as with interferon-β, it is sensible to screen patients who receive glatiramer acetate or signs of depression, and treat them appropriately if necessary.
Natalizumab: A retrospective analysis on the depression data of the phase III SENTINEL study on natalizumab showed that a significant number of patients who entered the trial without depression developed a positive score for depression during the trial. On the other hand, a more recent phase IV study analysing fatigue in patients treated with natalizumab showed better scores for depression among treated patients. The leaflet accompanying the drug warns of depression as a potential adverse effect.
Fingolimod: Fewer than 5% of patients using fingolimod develop depression, and depression is not among the 15 most common listed side effects of the drug. Studies analysing fingolimod's adverse events found no significant differences in development or worsening of depression However, the leaflet accompanying the drug lists depression as a potential adverse effect of the drug.
Patients with MS must be screened for depression before and during treatment with disease-modifying drugs.
Treating Depression in MS
Pharmacological treatment: Despite the high prevalence of depression in patients with MS and the potential danger of suicide, there are remarkably few methodologically sound papers on the subject. A Cochrane review identified only two studies, one using paroxetine and the other using desipramine. Each included only small patient numbers and short-term treatment. Adverse events were frequent, while several patients dropped out or were lost to follow-up. It is difficult to draw definite conclusions from these studies, but both drugs showed only a trend toward improving depression in MS. The confidence intervals were wide and there were no statistically significant differences between any of the drugs and placebo for any of the outcomes.
There have been open trials treating depression in MS using sertraline, moclobemide and fluoxetine, and duloxetine. Again, these were isolated studies with small numbers of patients and relatively short follow-up. The tendency to use selective serotonin receptor reuptake inhibitor is justified since tricyclic antidepressants could induce somnolence, reduce cognitive performance and exacerbate fatigue.
Non-pharmacological treatment: Individual cognitive-behavioural therapy, group psychotherapy, or sertraline were compared in an open trial on depressive patients with MS. There were no significant differences between these treatments, although the samples were small and the drop-out rate was around 20%. At least over the short term, individual cognitive behavioural therapy seems a good non-pharmacological alternative to treat depression in MS.
There are no evidence-based guidelines to treat patients with MS who present with depression; the choice depends upon the efficacy and tolerability of the drugs used to treat depression generally.
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