To compare the efficacy and safety of venlafaxine extended-release with amitriptyline for migraine prophylaxis in adults with episodic migraine.
Design
This was a prospective, single-center, open-label, parallel-group randomized controlled trial conducted at the Department of Neurology, Allied Hospital, Faisalabad, Pakistan. Eligible patients were randomized in a 1:1 ratio to receive either venlafaxine extended-release or amitriptyline for 12 weeks. Allocation was concealed using sealed opaque envelopes. Patients and treating physicians were not blinded because of different dosing schedules and expected adverse-effect profiles; however, endpoint assessment was performed by a clinician blinded to treatment allocation.
Settings and conduct
Department of Neurology, Allied Hospital, Faisalabad
City:
Faisalabad
Country:
Pakistan
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Adults aged 18 to 70 years; diagnosis of migraine according to International Headache Society criteria for at least 2 years; episodic migraine with 3 to 10 migraine attacks per month; ability to provide written informed consent.
Exclusion criteria:
Secondary headache disorders; major depression or psychiatric illness requiring medication; hypersensitivity to venlafaxine or amitriptyline; hepatic impairment; renal impairment; significant cardiac disease; pregnancy; lactation; concurrent monoamine oxidase inhibitor use; unwillingness to provide informed consent.
Intervention groups
Intervention Group 1
Group name:
Venlafaxine group
Intervention Group 2
Group name:
Amitriptyline group
Main outcome variables
Efficacy, defined as reduction in migraine severity by at least one grade on a 1 to 3 clinical severity scale compared with baseline.
General information
Reason for update
Acronym
VAM Trial
IRCT registration information
IRCT registration number:IRCT20260630070026N1
Registration date:2026-07-07, 1405/04/16
Registration timing:retrospective
Last update:2026-07-07, 1405/04/16
Update count:0
Registration date
2026-07-07, 1405/04/16
Registrant information
Name
Aasim Ali
Name of organization / entity
Allied Hospital Faisalabad
Country
Pakistan
Phone
+92 345 1129704
Email address
dr.aasimali1111@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2025-08-01, 1404/05/10
Expected recruitment end date
2026-01-31, 1404/11/11
Actual recruitment start date
2025-08-01, 1404/05/10
Actual recruitment end date
2026-01-31, 1404/11/11
Trial completion date
2026-04-30, 1405/02/10
Scientific title
Comparison of Efficacy of Venlafaxine and Amitriptyline in Migraine Prophylaxis: A Randomized Controlled Trial
Public title
Venlafaxine versus amitriptyline for prevention of migraine
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Adults aged 18 to 70 years; diagnosis of migraine according to International Headache Society criteria for at least 2 years;
Episodic migraine with 3 to 10 migraine attacks per month; ability to provide written informed consent.
Exclusion criteria:
Secondary headache disorders; major depression or psychiatric illness requiring medication; hypersensitivity to venlafaxine or amitriptyline; hepatic impairment; renal impairment; significant cardiac disease; pregnancy; lactation; concurrent monoamine oxidase inhibitor use; unwillingness to provide informed consent.
Age
From 18 years old to 70 years old
Gender
Both
Phase
4
Groups that have been masked
Outcome assessor
Sample size
Target sample size:
126
Actual sample size reached:
126
Randomization (investigator's opinion)
Randomized
Randomization description
Eligible participants were randomized in a 1:1 ratio using a computer-generated random number table. Allocation was concealed in sealed opaque envelopes. Participants were assigned to Group A receiving venlafaxine extended-release or Group B receiving amitriptyline.
Blinding (investigator's opinion)
Single blinded
Blinding description
Blinding of participants and treating physicians was not feasible because venlafaxine and amitriptyline have different dosing schedules and adverse-effect profiles. However, outcome assessment was performed by a clinician who was blinded to treatment allocation.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Faisalabad Medical Univeristy
Street address
Sargodha Road
City
Faisalabad
Postal code
38000
Approval date
2025-07-28, 1404/05/06
Ethics committee reference number
48.ERC/FMU/2025-26/105
Health conditions studied
1
Description of health condition studied
Episodic migraine
ICD-10 code
G43.9
ICD-10 code description
Migraine, unspecified
Primary outcomes
1
Description
Efficacy, defined as reduction in migraine severity by at least one grade on a 1 to 3 clinical severity scale compared with baseline.
Timepoint
Baseline and 12 weeks after start of treatment
Method of measurement
Clinical migraine severity scale: 1 = mild, able to work; 2 = moderate, unable to work; 3 = severe, bedridden.
2
Description
Frequency of treatment-emergent adverse events.
Timepoint
Assessed during follow-up visits at week 4, week 8, and week 12.
Method of measurement
Clinical assessment and adverse-event reporting, graded according to CTCAE version 5.0.
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group:
Category
Treatment - Drugs
2
Description
Intervention group:
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Department of Neurology, Allied Hospital, Faisalabad
Full name of responsible person
Dr. Mansoor Ul Hassan
Street address
Sargodha Road
City
Faisalabad
Postal code
38000
Phone
+92 345 1129704
Email
dr.aasimali1111@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Faisalabad Medical University
Full name of responsible person
Dr. Aamir Shoukat
Street address
Sargodha Road
City
Faisalabad
Postal code
38000
Phone
+92 345 1129704
Email
mukeshsharmakumar95@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Faisalabad Medical University
Proportion provided by this source
10
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Faisalabad Medical University
Full name of responsible person
Aasim Ali
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Neurology
Street address
Chak number 4 JB Reh
City
Faisalabad
Province
Punjab
Postal code
38000
Phone
+92 345 1129704
Email
dr.aasimali1111@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Faisalabad Medical University
Full name of responsible person
Aasim Ali
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Neurology
Street address
Sargodha Road
City
Faisalabad
Province
Punjab
Postal code
38000
Phone
+92 345 1129704
Email
dr.aasimali1111@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Faisalabad Medical University
Full name of responsible person
Aasim Ali
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Neurology
Street address
Sargodha Road
City
Faisalabad
Province
Punjab
Postal code
38000
Phone
+92 345 1129704
Email
dr.aasimali1111@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
Deidentified individual participant data will not be publicly shared because of participant confidentiality and because consent was not specifically obtained for public data sharing. Relevant study documents, including the study protocol and informed consent form, may be made available by the principal investigator on reasonable request and subject to institutional approval.
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available