Cotrip

What Is Cotrip?

Cotrip is an oral tablet of amitriptyline 10 / 25 / 50 / 75 mg from a WHO-GMP certified manufacturer, supplied in 30-180 tablet packs. Introduced in 1961 under the brand name Elavil; remains on the WHO Essential Medicines List for depression, neuropathic pain, and migraine.

Amitriptyline is a tertiary-amine tricyclic antidepressant (TCA) — 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 Amitriptyline 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; lower than the 75-150 mg used for depression)) is substantially lower than the antidepressant dose (75-150 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 Cotrip 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.
• Neuropathic pain — diabetic peripheral neuropathy, postherpetic neuralgia, post-stroke pain, trigeminal neuralgia (alternative to carbamazepine)
• Fibromyalgia — low-dose amitriptyline reduces pain and improves sleep
• Chronic tension-type headache — the only evidence-based preventive
• Post-traumatic headache
• Irritable bowel syndrome (pain-predominant) — low-dose
• Nocturnal enuresis in children (historical; rarely used now)
• Depressie — original FDA indication; now second- or third-line behind SSRIs

Cotrip 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.

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: 10-75 mg nightly
• Depression: 75-150 mg nightly

Toediening: swallow whole with water. Take at night — markedly sedating (H₁ antagonism is strong) — always dose at night. For most patients this is a therapeutic benefit (improves disrupted sleep that perpetuates migraine), but can cause morning hangover. 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 Cotrip:

• 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: Amitriptyline 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: Amitriptyline 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). If an elderly patient needs a tricyclic, nortriptyline is usually preferred over amitriptyline because of its lower anticholinergic burden.

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 Cotrip 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:

If amitriptyline side effects are dose-limiting, nortriptyline (Primox) is the classic alternative — amitriptyline’s active metabolite, same mechanism, roughly half the sedation and 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 Cotrip 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 Cotrip 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 150 mg nightly after 12 weeks, switch preventive.

Why am I so drowsy the next morning?

Amitriptyline 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 nortriptyline. Morning hangover usually improves over 2-4 weeks as tolerance develops.

Will Cotrip 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-HT_2C blockade. If weight gain is a concern, topiramate causes weight loss and propranolol is weight-neutral. Alternatively, nortriptyline causes slightly less weight gain than amitriptyline.

Is Cotrip 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 Cotrip with a triptan when a migraine attack strikes?

Yes — tricyclics are preventive, triptans are abortive. They work through different mechanisms. Take Cotrip 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 Cotrip?

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 Cotrip. Occasional small amounts (a glass of wine) are unlikely to cause problems; regular or heavy drinking is contraindicated.

Can I take Cotrip in pregnancy?

Amitriptyline 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 Cotrip?

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 Cotrip 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 Cotrip online?

You can buy Cotrip (amitriptyline 10 / 25 / 50 / 75 mg, 30-180 tablet packs) from MedsBase with discreet packaging and worldwide shipping.

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