Two prescription medications have large controlled trials behind them for canine separation anxiety: clomipramine and fluoxetine. Both beat placebo — but in every one of those trials, the placebo group received the same behaviour modification programme as the drug group. That single design detail is the most useful thing an Australian dog owner can know, and it is missing from nearly every article on this topic.
Supplements sit outside that prescription framework entirely. They can support a training plan; they cannot replace one. If you are building that plan and want a fully disclosed liquid to sit alongside it, our calming drops for dogs print every active with its amount per millilitre — so you and your vet can see exactly what your dog receives. A bottle is A$47, with free worldwide shipping: orders to Australia ship with duties and GST prepaid (DDP), nothing to pay on delivery.
With around 49% of Australian households now owning a dog (Animal Medicines Australia, Pets in Australia 2025) and many owners back in the office several days a week, separation distress is one of the most common behaviour problems vets in Australia hear about. Here is what the evidence actually supports.
What the prescription drugs were tested against
| Medication | Trial | Dogs | Design | Behaviour modification in placebo arm? |
|---|---|---|---|---|
| Clomipramine | King et al., Applied Animal Behaviour Science, 2000 | 95 | Randomised, double-blind, placebo-controlled, multicentre; standard dose 1–<2 mg/kg, low dose 0.5–<1 mg/kg, 2–3 months | Yes — all dogs received behavioural therapy |
| Fluoxetine | Simpson et al., Veterinary Therapeutics, 2007;8(1):18–31 (PMID 17447222) | 208 | Multicentre, double-blind, randomised parallel-arm; 1–2 mg/kg once daily for 6 weeks | Yes — fluoxetine plus behaviour management vs placebo plus behaviour management |
Clomipramine at the standard dose significantly reduced destruction, defecation, urination and vocalisation compared with placebo. Fluoxetine significantly improved destructive and rearranging behaviour and inappropriate urination.
Now read the last column again. Both trials show the benefit a drug adds on top of a structured training programme. Neither shows what a drug does instead of one — because that comparison was never run. Owners who expect a tablet to solve the problem alone are expecting something no published trial has ever demonstrated. In Australia, both medicines are prescription-only and your vet will advise which registered products are appropriate for your dog.
The trial doses, by body weight
Trial doses are published per kilogram. Here is the same information worked out for common Australian dog sizes — from a Cavoodle to a Kelpie to a Labrador — so you can follow what your vet prescribes.
| Dog weight | Clomipramine, standard trial dose (1–<2 mg/kg, twice daily) | Fluoxetine, trial dose (1–2 mg/kg once daily) |
|---|---|---|
| 5 kg | 5–10 mg per dose | 5–10 mg daily |
| 10 kg | 10–20 mg per dose | 10–20 mg daily |
| 20 kg | 20–40 mg per dose | 20–40 mg daily |
| 30 kg | 30–60 mg per dose | 30–60 mg daily |
| 40 kg | 40–80 mg per dose | 40–80 mg daily |
These are the amounts used in the published trials, provided so you can follow the conversation with your veterinarian — not a dosing instruction. Both drugs are prescription-only, both require a diagnosis, and neither should be started, stopped or adjusted without a vet.
What about devices, diffusers and wraps?
A randomised, placebo-controlled prospective clinical trial evaluated the Assisi anti-anxiety device (Calmer Canine), a targeted pulsed electromagnetic field unit, specifically for canine separation anxiety (PMC8720769). It is one of the very few separation-anxiety-specific device trials in existence, which tells you how thin this corner of the market is. Compression wraps, by comparison, have four controlled studies in total across all anxiety indications, out of 229 screened in a 2024 systematic review (Animals, 2024).
Australian shelves add pheromone diffusers and calming capsules to the mix. For context on cost, here is what the common options sold in Australia cost on 7 October 2026:
| Product | Format | Price seen in Australia |
|---|---|---|
| Pure Majesty Pets Calming Drops | Liquid; six disclosed actives per mL | A$47, free DDP shipping |
| Zylkene 225 mg (10–30 kg) | 30 capsules | A$95.14 RRP (Petstock) |
| Adaptil Calm diffuser refill | 48 mL refill | A$116.99 (Petbarn) |
| PAW Complete Calm Chews | 300 g chews | A$38.97 (Petstock) |
Zylkene is built on alpha-casozepine alone; Pure Majesty Calming Drops include alpha-casozepine (25 mg per mL) plus melatonin, L-theanine, chamomile, magnesium and vitamin B6 in one liquid — at roughly half the shelf price.
Where supplements honestly fit
No supplement is registered for separation anxiety, and none has been tested against it in a trial of the size run for clomipramine or fluoxetine. What some calming actives do have is controlled evidence for situational stress:
- Alpha-casozepine — in a randomised, fully blinded, placebo-controlled crossover study, twenty dogs given 15 mg/kg daily for six days before a standardised veterinary examination showed fewer fear-associated postures and lower observer-rated stress, though heart rate and heart rate variability were unchanged (J Vet Behav, 2025; see also Cannas et al., 2024).
- Melatonin — canine pharmacokinetics are established and it is widely used for sleep-wake timing and situational calm.
- L-theanine — studied in dogs, but the canine work is open-label with no placebo arm. Current research does not strongly prove this claim.
- Diphenhydramine (an antihistamine) — not a serious option here. In 56 dogs it produced no clinically appreciable sedation versus saline (JAVMA, 2005).
A supplement's realistic role in a separation-anxiety case is to take the edge off departures while the behaviour plan does the actual work, and to give a mildly affected dog something to lean on before the case escalates to prescription territory. In Australia, calming supplements that make no disease claims fall under the APVMA framework for nutritional products — which is why responsible brands say "supports calm" rather than promising to fix anxiety. If the dog learning to be alone is still a puppy, the age thresholds and lower starting amounts are set out in our guide to puppy calming drops.
Mild, moderate or severe: which lane are you in?
| Picture at home | Likely lane | Reasonable first step |
|---|---|---|
| Whines for a few minutes, then settles. No damage. | Mild departure stress | Departure-cue desensitisation, enrichment, a disclosed calming supplement |
| Vocalises for an hour, chews door frames or the screen door, occasional accidents. | Moderate | Structured behaviour plan with a qualified trainer; discuss medication with your vet |
| Bloodied paws, broken teeth, self-injury, escapes through windows or over the side fence. | Severe | Veterinary behaviour referral today. Prescription medication plus a plan. Supplements alone are not appropriate. |
Common mistakes owners make
- Treating the symptom list instead of the diagnosis. Destruction, house-soiling and vocalisation also appear in boredom, incomplete toilet training, noise phobia, pain and canine cognitive dysfunction. Filming the dog alone is the cheapest diagnostic you have — if the distress tracks summer storms or New Year's Eve fireworks rather than your departures, the fix is different, and our guide to the best calming supplement for thunderstorm anxiety covers it.
- Expecting week-one results. The fluoxetine trial ran six weeks; the clomipramine trial ran two to three months. SSRIs and tricyclics do not work on day two.
- Stopping the training once the tablets start. The training was in both arms of both trials. Removing it removes the foundation the drug effect was measured on top of.
- Punishing the mess. A panicking dog is not being spiteful, and correction after the fact adds fear to fear.
- Stacking supplements onto prescriptions silently. Melatonin and calming actives can interact with SSRIs, tricyclics, trazodone, gabapentin and MAO inhibitors. Tell your vet everything.
- Leaving an anxious dog in the car instead. RSPCA Australia warns that car temperatures can more than double outside temperatures — never a safe alternative to leaving a dog at home.
A four-week expectation setter
- Week 1: baseline. Film three departures. Note the exact minute distress starts — that number is your real progress metric, not "he seemed better".
- Week 2: departure cues decoupled (keys, shoes, bag) and absences kept below the distress threshold. A supplement given about 30 minutes before departures.
- Week 4: the point to compare footage against week one. If a prescription was started, it is likely still early — the trials needed six weeks or more.
- No change by week 4 on a supplement alone: that is your signal to escalate to a veterinary behaviourist rather than buy a different bottle.
Myth vs fact
| Myth | What the evidence says |
|---|---|
| "Getting a second dog fixes separation anxiety." | Separation anxiety is usually attachment to a specific person, not loneliness. There is no trial evidence that a companion dog resolves it. |
| "Medication is a last resort." | In the published trials, medication was combined with training from the start. For severe cases, delaying it prolongs the dog's distress. |
| "An antihistamine will get him through the workday." | Diphenhydramine sedated 56 dogs no better than saltwater. |
| "A calming supplement can fix separation anxiety." | No supplement is registered for it and none has been trialled against it at scale. Supportive at best — but genuinely useful in that role. |
When to call the vet today
Self-injury, broken teeth or torn nails from escape attempts, refusal to eat when alone, escape from a window or balcony, or anxiety that appeared suddenly in a previously settled adult or senior dog. That last one is not a training problem until pain and cognitive decline have been ruled out. The RSPCA Australia Knowledgebase and the AVA's Vet Voice site are good Australian starting points before your appointment.
For the over-the-counter landscape ranked by trial count, see our guide to best over-the-counter anxiety meds for dogs, and for the prescription and OTC picture side by side, best calming meds for dogs. The full category overview lives in our guide to calming dog supplements. If you prefer the single-ingredient route, start with melatonin for dogs.
What to look for in a supportive supplement
If you add one alongside a behaviour plan, insist on a label you can audit. Pure Majesty Pets calming drops for dogs disclose all six actives per millilitre — melatonin 3 mg, L-theanine 50 mg, alpha-casozepine 25 mg, water-soluble chamomile extract 25 mg, elemental magnesium 5 mg, vitamin B6 as P5P 0.5 mg — with no proprietary blend, so your vet can check every amount against the trial doses on this page before your dog takes a drop. Xylitol-free, made in North America with a Certificate of Analysis on every batch.
The label's starting guide for the melatonin amount is about 1 mg (~0.33 mL) for dogs under about 4.5 kg, about 1.5 mg (~0.5 mL) for roughly 4.5–11 kg, and about 3 mg (~1 mL) for roughly 12–45 kg, given around 30 minutes before a departure — always confirmed with your vet. Order Pure Majesty Pets Calming Drops for A$47 — free shipping to Australia, duties and GST prepaid, and start your four-week plan this week.
FAQ
What are the best separation anxiety meds for dogs?
Clomipramine and fluoxetine are the two medications with large randomised placebo-controlled trials in canine separation anxiety. Both are prescription-only, and in both trials every dog also received a behaviour modification programme.
How long do separation anxiety medications take to work?
The fluoxetine trial ran six weeks and the clomipramine trial ran two to three months. Expect weeks, not days, and keep the behaviour plan running throughout.
Can a calming supplement fix separation anxiety?
No supplement is registered for separation anxiety and none has been tested against it at the scale of the prescription drugs. Some actives have controlled evidence for situational stress and may support a training plan.
Does an antihistamine help a dog with separation anxiety?
A controlled study of 56 dogs found diphenhydramine produced no clinically appreciable sedation compared with saline. It is not a reasonable choice for separation distress.
Will getting another dog fix separation anxiety?
Usually not. Separation anxiety is typically attachment to a specific person rather than a fear of being alone in general, and there is no trial evidence that adding a companion dog resolves it.
Do Pure Majesty Pets Calming Drops ship to Australia?
Yes. Shipping is free worldwide, and orders to Australia ship with duties and GST prepaid (DDP), so there is nothing to pay on delivery. A bottle is A$47.
Veterinary disclaimer: This article is for general education and does not replace veterinary advice. Separation anxiety is a diagnosable condition — dose figures here are reported from published trials so you can discuss them with your veterinarian, not as instructions. Talk to your vet before starting any supplement or medication. Supplements are not intended to diagnose, treat or cure any disease.