Primox
Primox is nortriptyline 25 mg oral tablets — the active secondary-amine metabolite of amitriptyline, with the same mechanism but roughly half the anticholinergic and sedative burden. Used for migraine prevention, chronic tension-type headache, neuropathic pain, fibromyalgia, and depression. Preferred tricyclic in elderly patients and where amitriptyline side effects are dose-limiting. Start 10 mg nightly; titrate to 25-75 mg for migraine prevention. Full effect at 8-12 weeks.
✓ Medisch beoordeeld door Morgan Ellis — Apotheekonderzoeker · 8 jaar ervaring · Laatst beoordeeld: mei 2026
⚡ Quick Answer — What is Primox?
Primox bevat nortriptyline 25 mg from a WHO-GMP certified manufacturer — a secondary-amine tricyclic antidepressant (TCA) — the active metabolite of amitriptyline and the best-tolerated tricyclic for chronic migraine and neuropathic pain; the usual step-across when amitriptyline side effects are too severe. Although FDA-approved only for depression, tricyclic antidepressants have decades of evidence-based use at lower doses for migraine prevention, chronic tension-type headache, neuropathic pain, fibromyalgia, and chronic insomnia associated with pain. For preventie van migraine: start 10 mg nightly, titrate to 25-75 mg nightly (migraine-prevention range). Full effect at 8-12 weeks. Reduces monthly migraine days by ~50% in responders. Sedation is moderate (less H1 blockade than amitriptyline) — take at night but daytime hangover is less common — always dose at night. Anticholinergic burden is moderate — meaningfully less dry mouth, constipation, and cognitive effects than amitriptyline. This is the main reason to choose nortriptyline over amitriptyline. Contraindicated in recent MI, uncontrolled arrhythmias, QT prolongation, concurrent MAOI, narrow-angle glaucoma, severe hepatic impairment, and urinary retention / symptomatic BPH. Cardiac safety is the main consideration in patients over 50 — baseline ECG before starting is standard practice.
What Is Primox?
Primox is an oral tablet of nortriptyline 25 mg from a WHO-GMP certified manufacturer, supplied in 30-180 tablet packs. Introduced in the 1960s as Pamelor (VS) / Allegron (UK). Pharmacologically the desmethylated metabolite of amitriptyline — the body already converts amitriptyline into nortriptyline in vivo, so using nortriptyline directly bypasses the tertiary-amine side-effect burden.
Nortriptyline is a secondary-amine tricyclic antidepressant (TCA) — the active metabolite of amitriptyline — one of the classic drugs of modern psychopharmacology. In contemporary clinical practice, tricyclics have largely been displaced by SSRIs for first-line depression treatment, but they remain a cornerstone of neurology and pain medicine at doses well below the antidepressant range, particularly for migraine prevention, chronic tension-type headache, and neuropathic pain.
How Nortriptyline Prevents Migraine
The exact mechanism of tricyclic antidepressants in migraine prophylaxis is multi-modal:
- Serotonin + noradrenaline reuptake inhibition — enhances descending inhibitory pain pathways in the brainstem, reducing trigeminovascular signalling
- Central sensitisation reduction — blunts the spinal-cord and trigeminal-nucleus amplification that drives chronic daily headache
- NMDA receptor antagonism (weak) — reduces excitatory glutamate transmission
- Natriumkanaalblokkade — membrane-stabilising effect on hyperexcitable neurons
- H1 histamine blockade — explains the sedation, which indirectly helps migraine by improving sleep quality (disrupted sleep is a common migraine trigger)
- Anticholinergic effect — dries tears/mucus, not useful for migraine; explains the dry-mouth side effect
The migraine-prevention dose (25-75 mg nightly (migraine-prevention range)) is substantially lower than the antidepressant dose (75-100 mg nightly). This is important for three reasons: (1) lower doses minimise side effects, (2) the analgesic mechanism appears to be achieved at doses insufficient for antidepressant effect, and (3) it means Primox can be used for migraine prevention without necessarily being effective as an antidepressant. For patients with comorbid migraine and depression, doses toward the higher end address both conditions simultaneously.
Goedgekeurde en evidence-based toepassingen
- Migraineprofylaxe — off-label worldwide but endorsed as first-line in American Headache Society, American Academy of Neurology, and European Headache Federation guidelines. RCT evidence from Couch 2011 and the TOP-HAT trial.
- Chronic neuropathic pain — diabetic peripheral neuropathy, postherpetic neuralgia, post-stroke pain
- Fibromyalgia
- Chronic tension-type headache
- Smoking cessation (one of the few non-nicotine, non-bupropion options with RCT evidence)
- Depressie — original FDA indication; now typically reserved for treatment-resistant depression or when an SSRI has failed
- Melancholic / severe depression in older patients
Primox Dosage for Migraine Prevention
Tricyclic antidepressants are titrated from very low starting doses to minimise anticholinergic and sedative side effects. Patience is essential — reaching therapeutic effect usually takes 8-12 weeks.
| Stap | Dose (taken nightly) | Duration at this step |
|---|---|---|
| Week 1-2 | 10 mg nightly | Tolerability check |
| Week 3-4 | 25 mg nightly | Titration step |
| Week 5-8 | 50 mg (if tolerating and partial response) | Most common target dose |
| Week 9-12 | 75 mg (if still incomplete response) | Upper migraine-prevention dose |
| Maximum | 100 mg nightly | Rarely needed; if required, consider alternative agent |
Assess benefit at 8-12 weeks. Keep a migraine diary before starting and at week 12. A clinically meaningful response is ≥50% reduction in monthly migraine days. If no response at the target dose after 12 weeks, switch preventive.
Dose for other indications:
- Neuropathic pain: 10-50 mg nightly
- Depression: 75-100 mg nightly
Toediening: swallow whole with water. Take at night — moderate (less H1 blockade than amitriptyline) — take at night but daytime hangover is less common Take consistently at the same time each night for steady plasma levels.
Stopzetting: taper over 2-4 weeks (reduce by 10-25 mg every 5-7 days). Abrupt discontinuation of a tricyclic after several weeks of use causes a discontinuation syndrome — malaise, chills, sweating, sleep disturbance, GI upset, vivid dreams. It resolves over 1-2 weeks but is unpleasant. Never stop cold.
Baseline Tests and Monitoring
Before starting Primox:
- Baseline ECG — particularly over age 50, in any patient with cardiovascular history, and in anyone on other QT-prolonging medication. Tricyclics prolong the QT interval and can trigger ventricular arrhythmias in susceptible individuals. Avoid if QTc >450 ms.
- Electrolytes — hypokalaemia and hypomagnesaemia amplify QT prolongation risk. Correct first if abnormal.
- Liver function tests — tricyclics are hepatically metabolised; dose reduction needed in moderate hepatic impairment, avoid in severe.
- Glaucoma screen — narrow-angle glaucoma is an absolute contraindication (anticholinergic effect precipitates acute angle-closure attack).
- Urinary assessment in men over 50 — symptomatic BPH / urinary retention worsens with anticholinergic effect.
Bijwerkingen
Very common (>10%):
- Sedation, drowsiness, morning hangover — dose-related; partially adapts over 2-4 weeks
- Dry mouth, dry eyes (anticholinergic)
- Obstipatie (anticholinergic) — increase fibre and water; add a laxative if needed
- Gewichtstoename — average 1-3 kg over 6-12 months at migraine-prevention doses; more at antidepressant doses
- Postural hypotension and dizziness — more prominent in elderly; rise slowly from lying/sitting
Vaak (1-10%):
- Blurred vision (anticholinergic)
- Urinary hesitancy or retention (particularly men with BPH)
- Palpitations, tachycardia, mild QT prolongation
- Memory lapses, word-finding difficulty (dose-related; reversible)
- Tremor (fine; benign)
- Altered taste
- Sexual dysfunction (libido reduction, erectile dysfunction, anorgasmia) — dose-related
- Sweating
- Increased appetite
Zeldzaam maar belangrijk:
- QT prolongation / ventricular arrhythmia — particularly at higher doses, in overdose, or when combined with other QT-prolonging drugs. Tricyclic overdose is the most cardiotoxic of the common antidepressant-class overdoses; intentional ingestion is a medical emergency.
- Acuut glaucoom met gesloten kamerhoek in susceptible eyes
- Seizures at higher doses, particularly in patients with a lowered threshold
- Suïcidale gedachten — class warning for all antidepressants, particularly in the first 4 weeks and in patients under 25
- Serotonin syndrome — when combined with MAOIs or other serotonergic agents
- Hyponatriëmie (SIADH) — particularly in elderly
Contra-indicaties
- Recent myocardial infarction (within 3 months)
- Uncontrolled cardiac arrhythmia or heart block
- Known congenital long QT syndrome or QTc >450 ms
- Ernstige leverfunctiestoornis
- Concurrent use of MAOI or within 14 days of discontinuing an MAOI (phenelzine, tranylcypromine, moclobemide, selegiline, linezolid)
- Narrow-angle glaucoma
- Significant urinary retention
- Acute porphyria
- Hypersensitivity to tricyclic antidepressants
Zwangerschap: Nortriptyline is FDA Pregnancy Category C. Decades of observational data are broadly reassuring; no major congenital malformation signal. Neonatal withdrawal syndrome can occur with third-trimester use. For migraine prevention in pregnancy, propranolol is the first choice; tricyclics are a reasonable second option after failure of beta-blocker.
Borstvoeding: Nortriptyline passes into breast milk in small amounts. Generally considered compatible during breastfeeding; infant exposure is low.
Elderly (>65): tricyclics are on the Beers list of potentially inappropriate medications for older adults because of anticholinergic burden (falls risk, cognitive effects, constipation, urinary retention). Nortriptyline is the preferred tricyclic for elderly patients when one is required — its lower anticholinergic and sedative profile makes it safer than amitriptyline.
Geneesmiddelinteracties
- MAOIs (phenelzine, tranylcypromine, moclobemide, selegiline, linezolid) — contraindicated; serotonin syndrome risk. Separate by at least 14 days.
- SSRIs / SNRIs (fluoxetine, sertraline, paroxetine, citalopram, venlafaxine, duloxetine) — additive serotonergic effect; fluoxetine and paroxetine are strong CYP2D6 inhibitors and markedly raise tricyclic plasma levels (reduce Primox dose by 50%).
- Andere QT-verlengende geneesmiddelen (quinolone antibiotics, macrolides, methadone, antipsychotics, ondansetron, domperidone) — additive QT prolongation; avoid or monitor ECG
- Anticholinergic drugs (antihistamines, antispasmodics, oxybutynin, scopolamine) — additive anticholinergic burden; particularly problematic in elderly
- Sedating drugs (benzodiazepines, opioids, alcohol) — additive CNS depression
- Adrenergic drugs (direct-acting sympathomimetics, stimulants) — exaggerated response; avoid with phenylephrine in decongestants if on higher doses
- Warfarine — tricyclics can raise warfarin levels; monitor INR
- Tramadol — additive seizure and serotonin-syndrome risk; avoid
- Carbamazepine, fenytoïne — reduce tricyclic levels via CYP induction
- Alcohol — additive CNS depression and impaired driving; limit intake
Amitriptyline vs Nortriptyline — Which Tricyclic?
Amitriptyline is metabolised in vivo into nortriptyline (its active metabolite). Both work for migraine prevention; they differ in side-effect emphasis:
| Amitriptyline (Cotrip) | Nortriptyline (Primox) | |
|---|---|---|
| Chemical class | Tertiary amine | Secondary amine (active metabolite of amitriptyline) |
| Sedation | Strong (H1 blockade) | Matig |
| Anticholinergic burden | Strong | Moderate — ~half of amitriptyline’s |
| Postural hypotension | Vaak voorkomend | Less common |
| Migraine efficacy | Reference standard | Broadly equivalent |
| Beste voor | Migraine + poor sleep + pain — sedation is therapeutic | Migraine in patients where sedation or anticholinergic effects are limiting; elderly |
| Elderly appropriateness | Discouraged (Beers list) | Preferred tricyclic if one is needed |
If a full tertiary-amine tricyclic effect is needed (e.g. patient has marked insomnia as part of the migraine syndrome), amitriptyline (Cotrip) is the alternative — more sedating and more analgesic, at the cost of higher anticholinergic burden.
Opslag
Store below 25°C in the original blister pack. Protect from light. Keep out of reach of children — tricyclic overdose is potentially fatal in small children at relatively small doses.
Veelgestelde vragen
Will Primox work for my migraine if I’m not depressed?
Yes — the migraine-prevention mechanism (descending pain pathway modulation + sodium-channel blockade) works at doses well below the antidepressant range. ~50% of tricyclic users without depression still get a meaningful migraine reduction. Many patients are initially reluctant to take “an antidepressant” for migraine, but at 10-50 mg nightly the dose is functionally a neuromodulator, not an antidepressant.
How long before Primox starts preventing migraines?
Allow 8-12 weeks at target dose. Some patients see benefit earlier (at 4-6 weeks), but a fair trial is 12 weeks. Keep a migraine diary at baseline and at week 12. If no response at 100 mg nightly after 12 weeks, switch preventive.
Why am I so drowsy the next morning?
Nortriptyline has a long elimination half-life (12-36 hours for amitriptyline/nortriptyline). The sedation peaks overnight but can persist into morning. Mitigate by: (1) taking the dose earlier in the evening (e.g. 8 pm rather than bedtime), (2) reducing the dose if sedation is disabling, (3) switching to a less-sedating preventive like propranolol of topiramate. Morning hangover usually improves over 2-4 weeks as tolerance develops.
Will Primox make me gain weight?
Yes for some people — average 1-3 kg over 6-12 months at migraine-prevention doses. Mechanism: increased appetite via H1 and 5-HT2C blockade. If weight gain is a concern, topiramate causes weight loss and propranolol is weight-neutral. Alternatively, nortriptyline already has a better weight profile than amitriptyline.
Is Primox safe if I have heart problems?
Caution. Tricyclics prolong the QT interval and can trigger ventricular arrhythmias in susceptible individuals. Absolute contraindications: recent MI (within 3 months), uncontrolled arrhythmia, congenital long QT syndrome, QTc >450 ms on baseline ECG. Relative caution: any history of coronary disease, bundle branch block, or concomitant QT-prolonging medication. A baseline ECG is standard practice before starting in any patient over 50.
Can I take Primox with a triptan when a migraine attack strikes?
Yes — tricyclics are preventive, triptans are abortive. They work through different mechanisms. Take Primox nightly for prevention; take a triptan (sumatriptan, rizatriptan, zolmitriptan) as needed for breakthrough attacks. There is a theoretical serotonin-syndrome concern (2006 FDA advisory) but real-world data shows the combination is well-tolerated in clinical practice.
Can I drink alcohol on Primox?
Minimise alcohol intake. Tricyclics and alcohol are additive for sedation, cognitive impairment, and impaired driving. Alcohol is also a common migraine trigger, so reducing intake often improves migraine independent of Primox. Occasional small amounts (a glass of wine) are unlikely to cause problems; regular or heavy drinking is contraindicated.
Can I take Primox in pregnancy?
Nortriptyline has decades of observational pregnancy data with no major malformation signal (FDA Category C). For migraine prevention in pregnancy, propranolol is first choice; tricyclics are a reasonable second option if propranolol is contraindicated or ineffective. Neonatal withdrawal (irritability, feeding difficulty) can occur with third-trimester exposure but resolves within days.
How do I stop Primox?
Taper over 2-4 weeks (reduce by 10-25 mg every 5-7 days). Abrupt discontinuation causes a discontinuation syndrome: malaise, chills, sweating, sleep disturbance, GI upset, vivid dreams. Unpleasant but self-limiting over 1-2 weeks. Never stop cold.
Does Primox work for non-migraine headaches?
Yes — tricyclics are the only evidence-based preventive for chronic tension-type headache. They also help post-traumatic headache, medication-overuse headache (alongside withdrawal of the overused acute medication), and cervicogenic headache. Amitriptyline is the best-studied tricyclic across these indications; nortriptyline is broadly equivalent with better tolerability.
Where can I buy Primox online?
You can buy Primox (nortriptyline 25 mg, 30-180 tablet packs) from MedsBase with discreet packaging and worldwide shipping.
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