Evidence of Prescription of Antidepressants for Non-psychiatric Conditions in Primary Care

An Analysis of Guidelines and Systematic Reviews

Alain Mercier; Isabelle Auger-Aubin; Jean-Pierre Lebeau; Matthieu Schuers; Pascal Boulet; Jean-Loup Hermil; Paul Van Royen; Lieve Peremans

Disclosures

BMC Fam Pract. 2013;14(55)

Conclusions

Prescription of ADs was found to be useful for many non-psychiatric health conditions commonly encountered in primary care. Evidence against prescribing ADs was also found. The overall inconsistency of available information hindered precise assessment of the evidence. There remains much uncertainty as regards the role of prescribing ADs in therapeutic strategies, as well as the appropriateness and accuracy AD prescriptions. It is important to emphasise the difference between assessing the scientifically proven effect of an AD for a certain condition and the potential benefit of an AD at the right dose for a specific patient despite a lower level of evidence. Further studies are required to provide physicians more comprehensive knowledge and to improve patient care.

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Abbreviations
AD(s): Antidepressant(s); ALS: Amyotrophic lateral sclerosis; CDSR: Cochrane database of systematic reviews; Cismef: Catalogue and index of the French-language health resources; HAS: French "haute autorite de sante"; IBS: Irritable bowel syndrome; NICE: English National Institute for clinical excellence; NGC: National guideline clearinghouse; PC: Primary care; SMD: Standardized mean difference; TCA: Tricyclic agent; SSRI: Selective serotonin reuptake inhibitors; SNRIs: Selective norepinephrine reuptake inhibitors.

Authors' contributions
Conception of the idea for the study: AM. Development of the protocol: AM, IAA, JPL, MS, and PB. Data collection and extraction: AM, IAA, JPL. Critical assessment: AM, IAA, JPL, MS, and PB. PVR and LP participated in the design and coordination and helped to draft the manuscript. Writing of the manuscript: AM. All of the authors have read the draft critically, to make contributions, and have approved the final text.

Acknowledgements
The authors thank honorary Professor François Becret, and Pr Jacques Weber, and Pr Stefan Darmoni for their friendly support. We thank the Scientific Committee of the CIC-INSERM-Rouen University Hospital for reviewing the protocol corresponding to this study. Thanks to our English editor, Stephen Martin, for his proofreading and advices.

Funding
This work was not supported by any funding.

Table 1. Conditions included and excluded in the searches
Conditions included: primary care, non-psychiatric n = 44	Pain : n = 14
	Neuropathic pain, diabetic painful neuropathy, HIV-related neuropathy, trigeminal neuralgia, post herpetic neuralgia, phantom limb pain, central neuropathic pain, burning mouth syndrome, migraine, tension-type headaches (with or without drug abuse), fibromyalgia, non-specific low back pain, sciatica
	Other neurological conditions or symptoms: n = 9
	Dementia (agitation), Parkinson's disease (depression/agitation), emotionalism after stroke, prevention of depression after stroke, motor recovery after ischemic stroke, sleep disorders, restless legs syndrome, sialorrhea, tinnitus
	Urological conditions: n = 5
	Urinary incontinence, overactive bladder syndrome, urinary stress incontinence, erectile dysfunction, premature ejaculation
	Dependence: n = 2
	Smoking cessation, alcoholism
	General or non-specific conditions, general symptoms: n = 10
	"Chronic fatigue Syndrome or Asthenia or Fatigue", cancer-related fatigue, depression in physically ill people, musculoskeletal symptoms, unexplained complaints, somatoform disorders, treatment refusal, patient compliance, weight loss in adults with type 2 diabetes mellitus, pruritus
	Gynaecological conditions: n = 3
	Premenstrual syndrome, hot flashes/drug therapy, menopause
	Gastroenterological conditions: n = 1
	Functional colonic diseases: irritable bowel syndrome
Conditions excluded: ¹ n = 10	Narcolepsy, anorexia nervosa, isolated depression, dysthymic disorder, all isolated anxiety conditions, bulimia nervosa, amphetamine withdrawal, nocturnal enuresis, myotonia, cocaine dependence

Table 2. Assessment of AD usefulness
?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	-Neuropathic pain (neuralgia and painful polyneuropathy), diabetic painful neuropathy, central neuropathic pain, migraine, tension-type headaches, fibromyalgia
Useful ⁽¹⁾	-Urinary stress incontinence, premature ejaculation
n = 15	-Prevention of depression after stroke, emotionalism after stroke -Smoking cessation
	-Premenstrual syndrome, hot flashes/drug therapy, hot flashes during menopause
	-Irritable bowel syndrome
Possibly useful ⁽²⁾	-Post herpetic neuralgia, trigeminal neuralgia
n = 5	-Agitation in dementia, motor recovery after ischemic stroke
n = 5	-Overactive bladder syndrome
No proof of benefit ⁽³⁾	- Tension-type headaches with drug abuse, sciatica, Parkinson's disease, sleep disorders
n = 15	- pruritus
	- Asthenia- fatigue-chronic fatigue syndrome, cancer-related fatigue, depression in physically ill people
	- Unexplained complaints, somatoform disorders, treatment refusal, patient compliance, weight loss in adults with type 2 diabetes
Proof of no benefit ⁽⁴⁾	-HIV related neuropathy, phantom limb pain, burning mouth syndrome, non-specific low back pain, restless legs syndrome
n = 9	-Other urinary incontinence conditions, erectile dysfunction-Alcoholism/
n = 9	alcohol misuse
?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	-Musculoskeletal symptoms ⁽⁵⁾

(1) Recommended with evidence level mentioned or recent meta-analysis. (2) Mentioned without level of evidence, or second line treatment, or only RCTs. (3) Not enough or no data, apart from psychiatric condition. (4) No benefit mentioned in RCTs or reviews. (5) See fibromyalgia in Table 3.

Table 3. ADs in pain conditions 1
*Condition*	*AD treatment, role in strategy, rating of the recommendation*	*Comments and role of other treatments*
Neuralgia and painful polyneuropathy ^22–26	ADs recommended:	-Similar statements between guidelines:
	- TCAs: Amitriptyline first line (25–150 mg/day, Level A) Nortriptyline (alternative option) [22–26] NNT of 3.6 (95% CI: 3–4.5).	-Strong consensus for TCAs and venlafaxine.
	-SNRIs: Venlafaxine, fist line treatment (Level A) NNT of 3.1 Duloxetine: option	-Gabapentin, Pregabalin: also recommended as first-line treatments. TCAs are equally effective compared to non-AD drugs gabapentin (1200–3600 mg/day) and pregabalin (150–600 mg/day)
	SSRI: not recommended
Painful Diabetic Neuropathy (PDN) ^25–29	ADs recommended:	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
	-Duloxetine 60 mg and 120 mg daily, first-line, (Level A) The NNT for effectiveness was 1.3 (95% CI: 1.2- 1.5). This AD has on-label use for this condition [25,26,28]	Duloxetine: conflicting evidence between guidelines, just cited as a therapy for NP in the EFNS GL[24], and only for PDN in the Cochrane Review
	-Venlafaxine 150–225 mg/day; first line (no level mentioned)TCA : If other ADs contraindicated, Amitriptyline is an option	Venlafaxine might be added to gabapentin for a better response (Level C).
	SSRIs: not recommended
HIV-related neuropathies ²⁷	No AD treatment recommended	-Evidence not to prescribe any AD
HIV-related neuropathies ²⁷	No AD treatment recommended	- Recommended non-AD treatments: -lamotrigine (Level B), smoking cannabis (Level A), capsaicin patches (Level A)
Phantom limb pain ³⁰	No AD treatment recommended	Amitriptyline was not different from placebo
Trigeminal neuralgia ^25,26	-ADs are not first-line treatment	-Similar statements but lack of comparative trials to assess a precise role for TCAs and venlafaxine.
Trigeminal neuralgia ^25,26	-ADs recommended: TCA or venlafaxine are alternative treatments	First-line: carbamazepine (Level A) and oxcarbazepine (Level B)
Postherpetic neuralgia ^25,26	-ADs are not first-line treatments	-Similar statements but lack of comparative trials to assess a precise role for TCAs and venlafaxine
Postherpetic neuralgia ^25,26	- ADs recommended: TCA or venlafaxine are alternative treatments	-First-line: gabapentin/pregabalin (Level A)
Central pain ² ²⁴	-ADs are not first-line treatment	-Similar statements between guidelines
Central pain ² ²⁴	- ADs recommended: TCAs: Amitriptyline second-line (Level B)- SNRIs: Duloxetine and venlafaxine second choice (Level B)	-Pregabalin: first-line (level A)
Migraine and tension type headaches ^31–34	ADs recommended:	-Similar statements for TCAs, and SSRIs. Disagreement for the usefulness of venlafaxine
	-TCA: Amitryptiline 25–150 mg per day, (Level A).-Venlafaxine 75–150 mg was presented as an effective alternative to tricyclic antidepressants (Level B)	-TCA: In cases of TTH with associated drug abuse, the role of this treatment was only mentioned, with no rating, by the French HAS.
	SSRIs: not recommended
Sciatica, non-specific low back pain ^35–37	No AD treatments recommended	Only to be prescribed as an option in the event of associated depression (NICE)
Sciatica, non-specific low back pain ^35–37	No AD treatments recommended	Very weak evidence for TCAs observed by the French HAS (level C)
Fibromyalgia ³ ^28,38	ADs recommended:	Alternative pharmacological options: Gabapentin, tramadol
	SNRIs: Milnacipran 12.5 mg once daily, target dose of 50–100 mg two times per day
	-Duloxetine: 60 mg twice daily, -Venlafaxine could be prescribed -TCAs showed evidence
	SSRIs: not recommended
Burning mouth syndrome ³⁹	No AD treatments recommended	-Two RCTs showed no antidepressant effects

(1) Neuropathic pain is related to different treatment strategies and different conditions detailed in this table.
(2) Diffuse pain, refractory or recurrent pain, central pain, pain connected with multiple sclerosis, dysesthesia after stroke or paraplegia.
(3) See also comments in plain text: General or non-specific conditions and general symptoms.

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Evidence of Prescription of Antidepressants for Non-psychiatric Conditions in Primary Care

An Analysis of Guidelines and Systematic Reviews

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