Editorial · Knowledge

Botulinum Toxin for Chronic Migraine

What you will find here: the distinction between chronic and episodic migraine, the PREEMPT protocol (155–195 U across 31–39 points), its place in the treatment cascade per the 2018 DGN guideline, and the prerequisites for treatment. Booking and fee information on the treatment page.

Botulinum toxin for migraine is a specific therapy for a clearly defined group of patients — not for every migraine, and not as a first-line treatment. The key prerequisite is chronic migraine as defined by the DGN guideline, plus at least two previously unsuccessful prophylactic treatments. Those who meet these prerequisites benefit from an evidence-based treatment with a low side-effect profile — the background in anaesthesiology is central here, because 31–39 precise injections are placed multisegmentally.

Reading time · approx. 10 minutesAudience · patients with a confirmed migraine diagnosisLast reviewed · 17 May 2026

Contents

Chronic versus episodic migraine
Where BTX sits in the treatment cascade
The PREEMPT protocol in detail
Mechanism of action and efficacy
A pragmatic treatment trial in practice
The masseter muscle and bruxism comorbidity
Who treats — neurologist or anaesthesiologist?
Side effects and contraindications
What the treatment is not
In-depth questions
Evidence base

Section 1 · Indication boundaries

Chronic versus episodic migraine

The most important information before any BTX migraine treatment: botulinum toxin does not work for every migraine. The 2018 DGN guideline gives a clear recommendation — the therapy is effective only in chronic migraine. In episodic migraine, several large randomised trials (n > 1600 patients) demonstrated no significant efficacy over placebo.

Definition of chronic migraine

Diagnostic criterion	Threshold
Headache days per month	at least 15
of which migraine days	at least 8
Duration of symptoms	at least 3 months
Meeting the migraine criteria (ICHD-3)	unilateral or bilateral, pulsating, moderate to severe, aggravation by movement, nausea or photo-/phonophobia

Diagnostic prerequisite. The diagnosis of chronic migraine is made by a neurologist — typically via a headache diary kept for at least 3 months. Only on the basis of this documented diagnosis is BTX therapy indicated. A BTX treatment without prior neurological assessment would not be guideline-compliant.

Why BTX does not work in episodic migraine

The evidence is clear: in a meta-analysis published in 2009 with 1601 patients, no significant effect could be shown for the use of botulinum toxin in episodic migraine after stratification for different doses. In 2008, the American Academy of Neurology arrived at the assessment “probably ineffective.” Pathophysiological hypotheses explain this as follows: in chronic migraine there is a central sensitisation of the trigeminal nerve system — botulinum toxin presumably modulates these peripheral pain pathways better than it does the migraine mechanisms of episodic attacks.

Section 2 · Treatment cascade

Where BTX sits in the treatment cascade

The 2018 DGN guideline makes the sequence clear: botulinum toxin is not a first-line therapy. It is a procedure considered after unsuccessful medicinal prophylaxis.

Prerequisites before BTX therapy

At least two medicinal prophylactic treatments were carried out at an adequate dose over at least 2–3 months and were ineffective or not tolerated
Eligible first-line prophylactic agents include beta blockers (propranolol, metoprolol, bisoprolol), topiramate, flunarizine, valproic acid and amitriptyline
In addition, there must be a clinically relevant level of suffering — impaired quality of life, sick leave, risk of medication overuse
The patient must be comprehensively informed about effects, side effects and the realistic window of expectations

Newer alternative procedures

Since 2018, CGRP antibodies have additionally been available for migraine prophylaxis (erenumab, galcanezumab, fremanezumab, eptinezumab). They act via a different mechanism (blockade of the calcitonin gene-related peptide or its receptor) and are effective in both chronic and episodic migraine. In practice, many patients face the question: BTX or a CGRP antibody?

Practical decision logic. Both procedures are indicated after unsuccessful medicinal prophylaxis. CGRP antibodies often act faster (within 4 weeks), botulinum toxin fully after 2–3 treatment cycles. CGRP antibodies are monthly or quarterly injections — botulinum toxin every 12 weeks. The decision is typically made together with the treating neurologist, depending on comorbidities, prior treatments and patient preference.

Section 3 · Treatment protocol

The PREEMPT protocol in detail

The standardised treatment protocol is called PREEMPT — Phase III Research Evaluating Migraine Prophylaxis Therapy. It was established in two large randomised trials (PREEMPT 1 and 2, with a combined > 1600 patients) and is regarded as the standard today.

Total dose per cycle

155–195 IE

OnabotulinumtoxinA. The lower dose is the standard starting point, the higher dose if needed.

Injection points

31–39

Distributed across 7 anatomical muscle groups — skull, neck, shoulder girdle.

Per injection point

5 IE

Standard amount, occasionally adjusted with a “follow-the-pain” strategy.

Treatment interval

12 weeks

Duration of one cycle. The frequency is adjusted over time to the individual duration of effect.

The 7 treatment regions

Muscle group	Number of points (both sides)	Dose
Corrugator (glabella)	2 (1 pro Seite)	10 IE
Procerus (root of the nose)	1 (zentral)	5 IE
Frontalis (forehead)	4 (2 pro Seite)	20 IE
Temporalis (temple)	8 (4 pro Seite)	40 IE
Occipitalis (back of the head)	6 (3 pro Seite)	30 IE
Cervical paraspinal (neck)	4 (2 pro Seite)	20 IE
Trapezius (shoulder girdle)	6 (3 pro Seite)	30 IE
Standard total dose	31 points	155 IE

The additional 8 injection points (for a total dose of 195 U) follow the “follow-the-pain” strategy: where the patient localises the pain most strongly, further points are added in the frontalis, temporalis or occipitalis.

Anatomical precision is decisive. The injections are placed at defined anatomical points — not “somewhere in the painful region.” Each point is defined via palpable bony structures, the course of the muscle fibres and mid-pupillary lines. Careful marking before the treatment is standard. The treatment typically takes 20–30 minutes.

Section 4 · Mechanism of action

Mechanism of action and efficacy

Botulinum toxin type A acts at the neuromuscular junction — it cleaves the SNARE protein SNAP-25, which prevents the release of the neurotransmitter acetylcholine. In migraine, however, this mechanism is not sufficient on its own — because migraine is not a purely muscular disorder.

Three hypotheses for the mechanism

Modulation of pericranial pain pathways. Botulinum toxin inhibits not only the motor end plate but also the release of pain mediators (CGRP, substance P) at sensory nerve endings. This inhibition apparently occurs at the trigeminal pain pathways.
Reduction of peripheral and central sensitisation. In chronic migraine the trigeminal nerve system is overreactive. Botulinum toxin reduces the level of activation and thereby interrupts the transition into central sensitisation.
Reduction of muscle tone in the “pain chain.” Tension in the forehead, temples, neck and shoulders is a frequent companion of chronic migraine. Weakening these muscles reduces tonic pain triggers.

Efficacy in the trials

Endpoint	BTX group	Placebo
Reduction in headache days per month (24 weeks)	−8.4 days	−6.6 days
≥ 50 % reduction in headache days	approx. 47 %	approx. 35 %
Reduction in pain intensity	significant	—
Total side effects	62,4 %	51,7 %

A realistic window of expectations. Botulinum toxin is not a cure for migraine. It reduces the number of headache days by about 50 % in a subset of patients. The full effect only becomes visible after 2–3 treatment cycles (about 6–9 months). Patients who feel no effect after the first cycle should not give up — the first cycle is often described as a “settling-in phase.”

Clinical practice

A pragmatic treatment trial — clinical experience beyond the guideline

The 2018 DGN guideline is based on the randomised phase III trials (PREEMPT 1 and 2) and formally recommends OnabotulinumtoxinA only for chronic migraine. In the clinical practice of anaesthesiology, a somewhat broader picture emerges — which should be presented transparently.

Observations from the Ackermann practice

Episodic migraine with an aesthetic indication. Patients who have an aesthetic BTX treatment for glabellar or forehead lines and at the same time suffer from episodic migraine repeatedly report a reduction in attack frequency over time. Here the aesthetic treatment is the formal indication; any concomitant effect on the headaches is an anecdotal side effect — it is not confirmed in randomised trials.
Tension-type headache with an expression component. In patients with chronic tension-type headache and a clear tension component in the forehead, temples or neck, a BTX treatment trial can be sensible. Here too: no guarantee of efficacy from the evidence base, but clinical experience supports a trial.
Bruxism comorbidity. Many migraine and headache patients also show bruxism (grinding) or clenching at the same time — see the next section.

A realistic expectation. The pragmatic treatment trial is communicated openly: in the worst case the headache persists — but the treated regions are then wrinkle-free. In the best case, attack frequency is additionally reduced. This dual logic is the basis for honest counselling: patients pay for the aesthetic treatment and accept the non-guaranteed headache modulation as a possible side effect.

When a trial can be considered

Constellation	Pragmatic trial
Chronic migraine meeting the DGN criteria	Standard indication — PREEMPT protocol recommended
Episodic migraine + desire for aesthetic treatment	Aesthetic BTX with transparent counselling on the possible concomitant effect
Tension-type headache with an expression component	Treatment trial after individual consideration
Bruxism + headache comorbidity	Combination of the masseter + forehead / glabella

The decision is always made after a thorough consultation with an honest risk-benefit discussion and transparent fee information.

Comorbidity

The masseter muscle and bruxism — the frequent comorbidity

Migraine and bruxism frequently occur together. Studies show that more than half of all migraine patients simultaneously display signs of bruxism — grinding, clenching, pressure pain in the area of the temporomandibular joint, morning jaw fatigue.

Pathophysiological connection

The masseter muscle is trigeminally innervated (trigeminal nerve, V3). Tonic tension in this powerful chewing muscle leads to pain conduction along trigeminal pathways — the same pathways that are sensitised in migraine. Weakening the masseter can therefore produce three effects at once:

Functional effect: reduction of bruxism pressure, relief of temporomandibular joint complaints, protection of the tooth substance
Pain-modulating effect: reduction of tonic trigeminal activation — a possible contribution to migraine reduction
Aesthetic concomitant effect: a slim-face effect through reduced masseter hypertrophy

Co-treatment in practice

In migraine patients, the masseter is always palpated during the first consultation — hypertrophy, pressure pain and signs of bruxism are clear indicators for extending the treatment scheme. The typical dose is 25–40 U per side, distributed across 3 injection points. The treatment is often carried out in the same appointment as the PREEMPT protocol.

A separate indication. Bruxism treatment with BTX is a separate medical indication, independent of migraine. It is described in more detail on the teeth-grinding treatment page, including detailed information on the dosing logic, the typical course of treatment and statutory health-insurance reimbursement when a documented bruxism diagnosis exists.

Section 7 · Treating physician

Who treats — neurologist or anaesthesiologist?

The 2018 DGN guideline phrases this recommendation explicitly:

In this indication, OnabotulinumtoxinA should be used only by neurologists experienced in the diagnosis and treatment of chronic headache.

— DGN/DMKG S1 guideline 2018, treatment of the migraine attack and prophylaxis of migraine

What does this mean for our practice? Dr. Ackermann is a specialist in anaesthesiology, not a neurologist. This fact is presented transparently here — it is relevant, and the honest model is a collaborative one:

The collaborative model

Phase	Who	What
Diagnosis	Neurologist	History, headache diary over 3 months, diagnosis of chronic migraine per ICHD-3, exclusion of secondary causes
Treatment strategy	Neurologist	Treatment cascade, choice of medicinal prophylaxis, decision BTX vs. CGRP antibody after unsuccessful prophylaxis
BTX administration	Ackermann practice (or neurologist)	Precise injection per the PREEMPT protocol, complication management, assessment of progress
Follow-up and adjustment	Neurologist + Ackermann practice	Continued headache diary, cycle adjustment, decision on continuing therapy

Why the background in anaesthesiology is relevant

Even though the diagnosis is made by neurologists, the technical execution of the BTX migraine treatment is demanding. 31–39 precisely placed injections distributed across 7 anatomical regions, from the forehead to the shoulder girdle — this is multisegmental work that requires anatomical knowledge, confidence in palpation and dose-precise control. Anaesthesiology is the medical specialty that practises dose- and site-precise pharmacology in its daily work — from local anaesthesia to complex nerve blocks.

In the rare complication of pronounced neck-muscle weakness, the anaesthesiological routine is relevant: dosed agent control, experience with muscle pharmacology, immediate clinical assessment. That is the background that comes to bear here.

How the first contact typically unfolds. Patients often come with a wish for BTX migraine treatment — but without a prior neurological diagnosis. In that case the consultation explains that a neurological assessment should come first. The Ackermann practice refers to partner neurology practices in Erlangen, Nuremberg and the surrounding area. Once the diagnosis of chronic migraine is documented and at least two prophylactic treatments have failed, the BTX therapy can be carried out here.

Section 8 · Safety

Side effects and contraindications

The tolerability of BTX migraine therapy is well documented in the large trials. The main side effects are consequences of the muscle weakening in the treatment regions.

Common side effects

Observation	Frequency (BTX vs. placebo)	Duration
Neck pain	6.7 % vs. 2.2 %	1–3 weeks
Muscle-soreness-like complaints	occasional	3–7 days after injection
Neck-muscle weakness	rare	4–12 weeks
Headache after treatment	occasional	1–3 days
Cosmetic effects (facial expression)	common	10–12 weeks
Bruising at injection sites	common	3–7 days
Local irritation, pain	common, brief	1–2 days

Cosmetic side benefits. Since the PREEMPT protocol includes injections in the forehead, temples and glabella, a cosmetic carry-over effect can arise — less forehead lining, slight smoothing of the glabella. For many patients this is a welcome side effect. Anyone who wants a particularly expression-preserving treatment signals this during the consultation — the glabella and forehead points can be dosed lower if needed, without substantially compromising the anti-migraine effect.

Absolute and relative contraindications

Absolute: myasthenia gravis (botulinum toxin worsens the neuromuscular transmission disorder), pregnancy and breastfeeding (insufficient safety data), known allergy to botulinum toxin or carrier proteins
Relative: therapeutic anticoagulation (increased bruising risk, weigh up individually), known disorders of neuromuscular transmission (Lambert-Eaton, ALS, MG), treatment with aminoglycosides or other medications that potentiate neuromuscular transmission disturbance
Caution: severe cervical-spine conditions (injection into the cervical paraspinal region), local infections at injection sites

Section 9 · Indication boundaries

What the treatment is not

Five precise distinctions

It is not an acute treatment. BTX migraine therapy does not treat the single migraine attack. Anyone presenting with an acute migraine attack needs acute medication (a triptan, an NSAID), not a botulinum toxin injection.
It is not a first-line therapy. Before BTX comes into consideration, at least two medicinal prophylactic treatments must have been tried over an adequate period (at least 2–3 months per substance). BTX is an escalation, not a first offer.
It is not an aesthetic treatment. Even though forehead and glabella points are part of the PREEMPT protocol, the treatment is medically indicated. Billing follows different mechanisms than aesthetic BTX treatment; statutory health-insurance reimbursement is possible in individual cases when the prerequisites are met, but not guaranteed.
It is not primarily approved for episodic migraine. The randomised phase III trials show no significant superiority over placebo in episodic migraine — accordingly, the DGN recommendation is formally limited to chronic migraine. In clinical practice (see a pragmatic treatment trial), individual patients nonetheless experience a concomitant effect — this use would be off-label and requires transparent counselling as well as a clear main indication (typically: aesthetic).
It does not replace neurological follow-up care. Even during ongoing BTX therapy, regular neurological monitoring is important — headache diary, adjustment of acute medication, assessment of therapy efficacy.

Section 10 · In-depth questions

What patients want to understand more deeply

How do I know whether I have chronic migraine?

The diagnosis is made by a neurologist. Before the consultation, a headache diary kept for at least 3 months helps, documenting every headache episode: date, intensity (1–10), duration, character (pulsating/pressing), accompanying symptoms (nausea, photo-/phonophobia), triggers (stress, weather, hormonal cycle). When headaches occur on at least 15 days and at least 8 of these have the picture of a migraine — over at least 3 consecutive months — the diagnostic criteria are met.

How quickly does the treatment work?

The first treatment cycle often shows no full effect yet — many patients experience the full effect only after the second or third cycle (about 6–9 months after starting treatment). This delay is normal and is described in the trials. Anyone disappointed after the first cycle should not stop, but wait for the second cycle.

How long do I need to continue the therapy?

The DGN guideline recommends a therapy duration of at least 6–12 months where an effect is demonstrable. With a good effect, the treatment is typically continued over several years. There are indications from follow-up studies that the duration of effect lengthens with the cycles — the treatment frequency can decrease over time.

Does the health insurance cover the treatment?

When the prerequisites are met, statutory health-insurance reimbursement is possible in individual cases — provided the diagnosis of chronic migraine is neurologically documented and at least two medicinal prophylactic treatments demonstrably failed. The exact terms vary between insurers. In practice this is discussed individually — many patients choose the treatment as a self-pay service, some submit it to their insurer.

Can I combine BTX and CGRP antibodies?

Based on the current data, a combination has not been systematically investigated. In practice, combining is rare; a switch is more common — anyone who does not get a sufficient effect with BTX may switch to a CGRP antibody. Both procedures are modern standard therapies — the decision is made together with the treating neurologist.

What happens if I stop the treatment?

The migraine typically returns to its previous frequency range within 12–24 weeks. There is no “rebound effect” — the migraine does not become worse than before the treatment. A trial therapy break is possible over the long-term course and can be sensible on an individual basis.

Does BTX therapy affect my facial expression?

Since the forehead, glabella and temporalis regions are part of the PREEMPT protocol, cosmetic carry-over effects occur — less forehead lining, slight smoothing of the eye area. For many patients this is a pleasant side effect. Anyone who wants a particularly expression-preserving treatment signals this during the consultation — the glabella and forehead points can be dosed lower.

What to do about severe neck pain after the treatment?

Neck pain is the most common side effect (about 6.7 % of patients). It arises from the injection into the neck and trapezius muscles and typically subsides within 1–3 weeks. Helpful measures: warmth (heat pads, warm baths), gentle stretching exercises, an NSAID if needed. With very pronounced neck-muscle weakness, acute clinical assessment is important — the anaesthesiological routine in complication management is a concrete strength of the practice.

Section 11 · Evidence base

The scientific basis for the treatment

DGN/DMKG S1 guideline 2018 — treatment of the migraine attack and prophylaxis of migraine

Current German-language guideline on migraine therapy. Recommends OnabotulinumtoxinA at a dose of 155–195 units as prophylaxis in chronic migraine with and without overuse of pain and migraine medication. Explicitly excluded: efficacy in episodic migraine. Assesses the two large randomised PREEMPT trials as a sufficient evidence base.

Aurora SK et al., 2010 — PREEMPT 1 trial

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 30(7): 793–803. Large multicentre phase III trial with n = 679 patients. Defines the standardised injection scheme (155–195 U across 31–39 points) that is the standard today.

phase III RCT · establishes the standard protocol

Diener HC et al., 2010 — PREEMPT 2 trial

OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 30(7): 804–814. Complementary multicentre phase III trial with n = 705 patients. Confirms the results of the PREEMPT 1 trial and provides the basis for FDA and EMA approval.

phase III RCT · confirmatory trial

Aurora SK et al., 2014 — long-term effect over 5 cycles

OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program. Acta Neurol Scand 129(1): 61–70. Shows that the effect increases continuously over 5 consecutive treatment cycles — the full therapeutic effect establishes itself over 12–15 months.

long-term observational study

Jackson JL et al., 2012 — meta-analysis of all BTX migraine studies

Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. JAMA 307(16): 1736–1745. Comprehensive meta-analysis of all published studies on BTX in migraine and headache. Confirms: significant effect in chronic migraine, no effect in episodic migraine — the basis of the modern indication boundary.

meta-analysis · highest level of evidence

The works cited here form the scientific foundation of the DGN recommendation. The evidence is comprehensive: PREEMPT 1 and 2 together comprised > 1380 patients with chronic migraine, and pooled analyses reach patient numbers > 1115. The 2018 guideline was developed in an iterative Delphi process by 20 authors.

Would you like to discuss the treatment in person?

The treatment page with the treatment process, prerequisites and fee information is here:

Migraine treatment · Overview

For an overview of all treatments with botulinum toxin type A, see the category page.

For patients from the Erlangen area: botulinum toxin treatment near Erlangen.

Author and last review

Dr. med. Thomas Ackermann

Specialist in Anaesthesiology · Medical Director, Harmonie der Ästhetik

BTX migraine therapy requires two components — a sound neurological diagnosis and a precise, multisegmental administration of 31–39 injections across 7 anatomical regions. For the diagnosis we refer to partner neurology practices in the region; the administration is in qualified hands here. The background in anaesthesiology is the daily craft for exactly this kind of dose- and site-precise pharmacology. This page was last reviewed on 17 May 2026.

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