Copyright
©The Author(s) 2015.
World J Neurol. Mar 28, 2015; 5(1): 17-38
Published online Mar 28, 2015. doi: 10.5316/wjn.v5.i1.17
Published online Mar 28, 2015. doi: 10.5316/wjn.v5.i1.17
Depressed mood most of the day, nearly every day |
Markedly diminished interest or pleasure in all or almost all activities |
Significant weight loss when not dieting or weight gain |
Insomnia or hypersomnia nearly every day |
Psychomotor agitation or retardation |
Fatigue or loss of energy |
Feelings of worthlessness or excessive or inappropriate guilt |
Diminished ability to think or concentrate, or indecisiveness |
Recurrent thoughts of death or suicidal ideation |
Class | Mechanism of action | Generic name (trade name) | Dose range (mg/d) |
Older antidepressants | |||
Mixed serotonin and norepinephrine reuptake inhibitors | |||
First-generation tricyclic antidepressants | Inhibit neuronal reuptake of norepinephrine and serotonin | Amitriptyline (elavil) Clomipramine (anafranil) Doxepin (adapin) Imipramine (tofranil) Trimipramine (surmontil) Protriptyline (vivactil) Lofepramine | 100-300 100-250 100-300 50-300 100-300 75-200 15-60 |
Second-generation tricyclic antidepressants | Inhibit neuronal reuptake of norepinephrine and serotonin | Desipramine (norpramin) Nortriptyline (pamelor) | 100-300 50-150 |
Tetracyclic antidepressants | Inhibit neuronal reuptake of norepinephrine and serotonin | Maprotiline (ludiomil) | 100-200 |
Amoxapine (asendin) | 50-300 | ||
Heterocyclic agents Triazolopyridines | Mixed serotonin effects: Serotonin (5-HT2A) receptor blockade with serotonin reuptake inhibition | Trazodone (desyrel) | 150-400 |
Monoamine oxidase inhibitors | Nonselective inhibitor of monoamine oxidase A and B | Phenelzine (nardil) Tranylcypromine (parnate) Selegiline (eldepryl) | 60-90 20-60 5-10 |
Newer antidepressants | |||
Selective serotonin reuptake inhibitors | Selectively inhibit the reuptake of 5HT at the presynaptic neuronal membrane. Sertraline also markedly inhibits dopamine reuptake | Fluoxetine (prozac) Fluvoxamine (luvox) Paroxetine (paxil) Sertraline (zoloft) Citalopram (celexa) Escitalopram (lexapro) | 20-60 100-300 20-50 50-200 20-40 5-20 |
Serotonin and noradrenaline reuptake Inhibitors | Potent inhibitors of 5HT and norepinephrine uptake; weak inhibitors of dopamine reuptake | Venlafaxine (effexor) Milnacipran (savella) Duloxetine (cymbalta) | 75-350 12.5-100 60 |
Norepinephrine reuptake inhibitors | Noradrenaline reuptake inhibitor. Inhibits norepinephrine reuptake without inhibiting serotonin reuptake | Viloxazine Reboxetine (edronax) Atomoxetine (strattera) | 150-300 4-8 40-80 |
Reversible inhibitors of monoamine oxidase A | Selective, reversible inhibitors of monoamine oxidase A: resulting in increased concentrations of NE, 5-HT, and dopamine in synapse | Moclobemide Brofaromine | 300-600 75-150 |
5HT2 receptor antagonists/reuptake inhibitor serotonin modulators | Mixed serotonin effects. Inhibition of the reuptake of serotonin and selective postsynaptic 5-HT2A blockade | Nefazodone (serzone) Desvenlafaxine (pristiq) Ritanserin | 300-600 50 mg once daily 5-10 |
5HT1a receptor agonists | Partial agonist of serotonin 5-HT1a | Gepirone, ipsapirone, tandospirone, felsinoxan | |
α2-noradrenergic antagonists | Complex action on serotonin and noradrenaline via Serotonin (5-HT2A and 2C) receptor blockade and presynaptic α2-receptor blockade | Mirtazapine (remeron) | 15-45 |
GABA-mimetics | GABAA and GABAB receptor agonists | Fengabine | 900-1800 |
Dopamine reuptake inhibitors | Increases activity of norepinephrine and dopamine only; no significant effect on serotonin | Buproprion (wellbutrin) | 200-450 |
Melatonin receptor agonists | Melatonin MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist | Agomelatine (valdoxan) | 25-50 |
Herbal remedy: Hypericumperforatum/ St. John’s wort | Unclear: inhibits the reuptake of several neurotransmitters, including 5HT, NE, dopamine, and γ-aminobutyric acid | Hypericum perforatum | 300-900 |
Stage of PD/type of patients | No. of patients/ | Prevalence of depression/ depressive symptoms | Prevalence of other neuropsychatric | Ref. |
sample size | symptoms | |||
Outpatients, non-fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists) | 90 | Major depression in 21.1% (vs in 3.3% controls) | Panic disorders in 30% (vs 5.5% in controls) Dystimia in 18.8% (vs 4.4% in controls) | [26] |
Outpatients with established PD | 100 | Major depression in 35% | [35] | |
Patients with PD presenting with non-motor symptoms. Retrospective study of pathologically-proven PD | 91 | Depression in 2.5% | Anxiety in 3.9% | [33] |
Outpatients with established PD | 50 | Major depression in 42% (vs 10% of geriatric patients) | [28] | |
Nondemented patients with moderate to severe PD | 111 | Depression in 26.1% Subthreshold depression in 28.8% | [27] | |
Early untreated PD | 175 | Depression in 37% | Apathy in 27% Sleep disturbance in 18% Anxiety in 17% | [29] |
New-onset PD patients | 685 | Depression in 72% (developed depression within ten years of symptomatic PD onset) | [36] | |
Outpatients with established PD | 1086 | Major depression in 15.6% | [37] | |
Outpatients with established PD Outpatients with established PD Outpatients with established PD | 1449 1449 150 | Depression in 25% Depression in 33.6% Depression in 43% Depression without apathy in 13% | Anxiety in 20% Dementia in 29% Psychotic syndromes in 12.7% Sleep disturbances in 49% Apathy only in in 17% Apathy + depression in 43% | [38] [39] [40] |
Non-demented PD subjects | 105 | 38% borderline depression Major depression in 4.8% | [30] | |
Non-demented PD subjects | 450 | Depressive symptoms in 40% (vs 10% of controls) | Probable anxious signs in 51% (vs 29% of controls) | [41] |
Patients with established PD | 256 | Minor depression in 36.3% Major depression in 12.9% | [42] | |
Patients with established PD | 360 | Depression in 41.3% | Only apathy in 23% Apathy + depression in 36.9% | [43] |
Patients with established PD | 202 | Depression in 37.3% | Anxiety in 31.3%, Dementia in 25.3% Excessive daytime sleepiness in 59.4% | [31] |
Patients with established PD | 513 | Depression in 8.6% | Anxiety alone in 22.0% Anxiety + depressive symptoms in 8.6% | [44] |
Outpatients with established PD | 158 | Depression in 11% to 57% (depending on the definition of depression) | [45] | |
Outpatients with established PD New-onset PD patients | 639 221 | Depression in 66% Major depression in 9.9% (developed depression over 3-4 yr) | [34] [46] | |
Outpatients with established PD | 1449 | Depression in 18.8% | Dementia in 13.9% had Dementia + depression in 14.3% | [47] |
Non-demented PD subjects Early stage PD | 95 36 | Depression in 28% Depression in 36.1% | Anxiety in 27% Obsessive-compulsive symptoms in 52.8% Somatization in 66.7% | [48] [49] |
Outpatients with established PD | 117 | Depression in 56% | Anxiety in 55% | [50] |
Patients with established PD (ambulatory and home residents) | 886 | Depression in 24.4% | 28.4% dementia (20.6 % of ambulatory and 85.7 % of home residents) | [51] |
PD patients with mild cognitive impairment | 104 | Depression in 40.4% (vs 16.6% in controls) | Subjective memory complaints 16.3% (vs 7.7% of controls) | [32] |
Non-demented PD subjects | 115 | Major depression in 28.7% Subthreshold depression in 26.10% | [52] |
Drug | Study design | Sample size | Study objectives | Outcomes | Adverse effects | Ref. |
Fluoxetine | 23 | Effects of fluoxetine (up to 40 mg/d) on motor performance | 20/23 patients experienced no worsening of parkinsonism | [167] | ||
Fluoxetine, fluvoxamine, citalopram, and sertraline | Open-label prospective study | 62 depressed patients with PD (without dementia or motor fluctuation) (15 patients received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline) | Effects of SSRIs on motor performance and depressive symptoms | ↓↑ UPDRS scores Significant improvements in depression with all SSRIs | [168] | |
Fluoxetine/amitriptyline | Randomized study | 77 patients with PD (37 received fluoxetine and 40 received amitriptyline) | Comparing fluoxetine (20-40 mg/d) and amitriptyline (25-75 mg/d) at low doses on depressive symptoms | Amitriptyline better controlled depression at 3, 6, 9 and 12 mo, respectively | 15% abandoned amitriptyline because of side effects | [137] |
Fluoxetine | Prospective, controlled, open-label study | 18 patients with PD and mild depression without dementia | Influence of fluoxetine (20 mg/d) on motor functions | Significant improvements in scores of depression and Parkinson’s disability | [174] | |
Paroxetine | To assess the tolerability of paroxetine (20 mg once per day) | Improved depression UPDRS scores ↓↑ | Reversible worsening of tremor in one patient | [171] | ||
Paroxetine | 65 outpatients with PD and depression | To assess the tolerability of paroxetine (10-20 mg once per day) | Improved depression | 20% stopped paroxetine because of adverse reactions Increased “off” time and tremor in 2 patients (reversible) | [170] | |
Paroxetine CR/nortriptyline | Randomized, placebo controlled trial | 52 patients with PD and depression | To evaluate the efficacy of paroxetine CR and nortriptyline in treating depression | Nortriptyline was superior to placebo for the change in depressive scores Paroxetine CR was not | [140] | |
Paroxetine/venlafaxine | Randomized, double-blind, placebo-controlled trial | 115 subjects with PD | To compare efficacy and safety paroxetine and venlafaxine extended release in treating depression in PD | Both paroxetine and venlafaxine XR significantly improved depression UPDRS scores ↓↑ | [173] | |
Citalopram | 46 non-demented patients with PD. 18 depressed and 28 non-depressed | Effect of citalopram on motor and nonmotor symptoms of depressed and nondepressed patients with IPD | Improvement in mood in 15/16 patients Motor performance ↓↑ Improved bradykinesia and finger taps in patients with and without depression | [169] | ||
Citalopram | Prospective, open label trial | 10 patients with PD and major depression, without dementia | Effects of citalopram on depressive symptoms | Significant improvement in depression and in anxiety symptoms and functional impairment | [175] | |
Escitalopram | Open-label study | 14 Parkinson’s disease patients with major depression | Effects of escitalopram on depressive symptoms | ↓ in depressive symptomatology score (response and remission rates were only 21% and 14%) | [176] | |
Sertraline | Open-label pilot study | 15 patients with PD and depression | To evaluate the safety and efficacy of sertraline to treat depression in PD | Significant improvement in depression UPDRS scores ↓↑ | Side effects in 1/3 2 patients discontinued sertraline | [177] |
Sertraline Sertraline | 54 PD patients with depressive disorders 374 PD patients with depressive symptoms | Comparing efficacy of sertraline in the usual formulation and in the liquid oral concentrate Long-term effects of sertraline on motor status | Improved depression on both formulations Improved clinical global impression-severity of illness scale Improved UPDRS ↓ Anxiety ↓ Depression | 8% discontinued medication for adverse events (gastrointestinal) Worsening of tremor in some patients | [179] [178] | |
Sertraline/amitriptyline | Prospective single-blind randomized study | 31 patients with PD and depression | Assessment of the effect of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life | ↓ Depression by both drugs Sertraline improved quality of life ↓↑ UPDRS scores | [138] | |
Sertraline/pramipexole | Randomized trial | 67 outpatients with PD and major depression but no motor fluctuations and/or dyskinesia | To compare pramipexole with sertraline | Both sertraline and pramipexole improved depression Pramipexole caused more recovery compared to sertraline (60.6% vs 27.3%) Pramipexole improved UPDRS motor subscore | 14.7% withdrew from the sertraline group | [99] |
Nefazodone/fluoxetine | A pilot randomized trial | Depressed patients with PD | To assess the effect of nefazodone on extrapyramidal symptoms in depressed PD patients | Nefazodone significantly improved UPDRS score Both nefazodone and fluoxetine were equally effective in treating depression | [185] | |
Trazodone | Randomized trial | 20 PD patients with and without depression | To test the ability of trazodone to improve depression and motor function | Significantly improved depression Improves motor function in depressed patients | [186] | |
Venlafaxine | Prospective study | 14 non-fluctuating PD patients with depression | To investigate the therapeutic efficacy of venlafaxine | Improved depression scores UPDRS scores ↓↑ | [195] | |
Atomoxetine, a SNRI | Randomized placebo- controlled study | 55 subjects with PD depression atomoxetine or placebo | To assess efficacy of atomoxetine (80 mg/d) in treating depression | Failed to improved depression Improved global cognition Improved daytime sleepiness | [196] | |
Duloxetine | Non-comparative, open-label, multi-center study | 151 patients | To evaluate the tolerability, safety, and efficacy of duloxetine 60 mg once daily in PD patients with major depressive disorder | Improved depressive scores Improved activities of daily living Tremor ↓↑ Rigidity ↓↑ | 8.6% discontinued the study due to side effects | [197] |
- Citation: Abdel-Salam OM. Prevalence, clinical features and treatment of depression in Parkinson’s disease: An update. World J Neurol 2015; 5(1): 17-38
- URL: https://www.wjgnet.com/2218-6212/full/v5/i1/17.htm
- DOI: https://dx.doi.org/10.5316/wjn.v5.i1.17