Antidepressants

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Antidepressants are widely used in human medicine to treat depression, anxiety disorders, and other mental conditions. They include various substance groups, such as selective serotonin reuptake inhibitors (SSRIs, e.g., sertraline, fluoxetine), tricyclic antidepressants (TCAs, e.g., amitriptyline), serotonin-norepinephrine reuptake inhibitors (SNRIs, e.g., venlafaxine), and monoamine oxidase inhibitors (MAOIs). Due to their increasing prevalence in households, accidental ingestion by pets occasionally occurs, which can lead to severe poisoning. Dogs, in particular, but also curious cats, are affected. Owners should therefore be aware of the potential dangers of these medications for their animals and take preventive measures.

The most important facts at a glance

Antidepressant poisoning in dogs and cats is a medical emergency that requires rapid action. The different classes of antidepressants – tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs) – can cause varying but potentially life-threatening poisoning symptoms. TCAs are considered particularly dangerous due to their narrow therapeutic window and their effect on multiple neurotransmitter systems.

The symptoms of antidepressant poisoning primarily affect the central nervous system and the cardiovascular system. Diagnosis is based on anamnesis, clinical presentation, and supportive examinations such as ECG and laboratory analyses. Therapy includes decontamination measures, symptomatic treatment, and intensive care monitoring. With early and adequate treatment, the prognosis is good in most cases. Preventive measures such as safe storage of medications are crucial to avoid poisoning incidents.

Causes, development and progression

The most common cause of antidepressant poisoning in dogs and cats is the accidental ingestion of medication left open or dropped. Dogs, who often mistake medication for treats, are particularly at risk. While cats are less frequently affected, they often react more sensitively due to their unique metabolism.
Even small amounts of antidepressants can be toxic. First symptoms usually appear within one to four hours after ingestion and often worsen rapidly. The course depends heavily on the substance group and the amount ingested. Poisoning with tricyclic antidepressants is often more severe and life-threatening than with SSRIs.

Mechanism of action

Tricyclic antidepressants have low selectivity, meaning they also interact with other receptors, which can lead to diverse symptoms in intoxications.
Their anticholinergic, central nervous, and cardiovascular effects are prominent.
(anticholinergic = acting against the neurotransmitter acetylcholine)
Furthermore, there are many interactions with other medications.
The therapeutic window of these antidepressants is also narrow, so toxic effects can occur even with the ingestion of small amounts.

Antidepressants act on the nervous system through complex mechanisms. They increase the concentration of certain neurotransmitters such as serotonin, norepinephrine, and dopamine in the synaptic cleft by blocking their reuptake. This leads to a toxic overstimulation of the central and autonomic nervous systems.

  • Tricyclic antidepressants (TCAs) additionally block muscarinic, adrenergic, and histaminergic receptors, which can lead to cardiac arrhythmias, hypotension, and seizures.
  • SSRIs and SNRIs primarily lead to serotonin overstimulation (“serotonin syndrome”) with neurological and autonomic symptoms.
  • MAO inhibitors also indirectly increase serotonin and norepinephrine levels and can cause dramatic symptoms, especially in combination with other medications.

Supplements

Antidepressants comprise several drug classes with different targets in the central nervous system. In toxic doses, they can lead to severe neurological, cardiovascular, and metabolic effects in animals. The most common drug groups in intoxications in dogs and cats are:

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

Examples: Fluoxetine, Sertraline, Paroxetine

Mechanism of action:
SSRIs block the reuptake of serotonin (5-HT) from the synaptic cleft, leading to an excessive increase in serotonin concentration.

  • In toxic doses → Serotonin Syndrome:

    • Overexcitation of the serotonergic system in the CNS and periphery

    • Symptoms: Tremor, hyperactivity, ataxia, seizures, hyperthermia, tachycardia, mydriasis

2. Tricyclic Antidepressants (TCAs)

Examples: Amitriptyline, Clomipramine

Mechanism of action:

  • Inhibition of norepinephrine and serotonin reuptake

  • Anticholinergic effects due to blockade of muscarinic acetylcholine receptors

  • Antihistaminic effect

  • Membrane-stabilizing effect on cardiac muscle cells → risk of cardiac arrhythmias

Toxic effects:

  • Cardiotoxicity: QT prolongation, ventricular arrhythmias

  • CNS symptoms: Seizures, altered consciousness

  • Anticholinergic signs: Mydriasis, tachycardia, dry mucous membranes, urinary retention

3. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Examples: Venlafaxine, Duloxetine

Mechanism of action:

  • Increase in serotonin and norepinephrine in the CNS

  • In toxic doses, also serotonin syndrome, hypertension, neurological symptoms

4. Monoamine Oxidase Inhibitors (MAOIs)

Example: Selegiline (rare)

Mechanism of action:

  • Inhibition of the enzyme monoamine oxidase → reduced breakdown of serotonin, norepinephrine, and dopamine

  • In toxic doses: massive CNS overstimulation, hypertension, seizures

Symptoms of intoxication

The time between ingestion and the first signs of intoxication (latency period) is short. Untreated, death can occur in small animals within an hour.
In both dogs and cats, the antidepressant imipramine, when ingested orally at just 100 mg/kg body weight, can lead to signs of intoxication.
General symptoms include:

  • Dizziness
  • Vomiting
  • Drowsiness
  • Respiratory depression
  • Lethargy
  • Anxiety
  • Aggressive behavior
  • Constipation
  • Urinary retention
  • Hypokalemia and hyponatremia

Damage to the central nervous system manifests as

  • Coordination disorders
  • Muscle tremors
  • Seizures
  • Unconsciousness

In the cardiovascular system

  • Pronounced arrhythmias
  • Ventricular fibrillation
  • Drop in blood pressure leading to
  • Cardiogenic shock

Symptoms can vary depending on the drug class but show typical patterns:

Symptoms in dogs:

Tricyclic antidepressants (e.g., Amitriptyline):

  • Apathy, lethargy, or massive restlessness
  • Vomiting, diarrhea
  • Dilated pupils (mydriasis)
  • Cardiac arrhythmias (arrhythmias, tachycardia)
  • Respiratory problems, hyperthermia (elevated body temperature)
  • Tremors, seizures, coma

SSRI/SNRI (e.g., Fluoxetine, Sertraline, Venlafaxine):

  • Hyperactivity, nervousness, restlessness
  • Excessive salivation, vomiting
  • Coordination disorders (ataxia), muscle tremors
  • Increased heart rate, blood pressure fluctuations
  • Seizures, serotonin syndrome (high fever, tremors, restlessness, neurological disorders)

Symptoms in cats:

Cats show similar symptoms but are often more sensitive:

  • Salivation, vomiting, loss of appetite
  • Apathy or hyperactivity, restlessness
  • Neurological symptoms such as ataxia, tremors
  • Cardiac arrhythmias, rapid breathing rate
  • Rapid development of seizures, serotonin syndrome, hyperthermia
  • Rapid deterioration of general condition possible

Diagnosis

The diagnosis of antidepressant poisoning is primarily based on the anamnesis and the animal’s clinical presentation. Crucial information includes whether the owner knows of the animal’s potential access to antidepressants, as well as the type and amount of the potentially ingested substance. In cases with an unclear history, the characteristic symptom pattern can provide clues, with the combination of cardiovascular and central nervous disorders being particularly indicative of TCA poisoning.

The clinical examination includes assessment of vital parameters, neurological examination, and cardiovascular evaluation. Laboratory tests such as blood count, electrolytes, liver, and kidney values can provide indications of organ damage or metabolic disorders. An ECG is particularly important for assessing cardiac arrhythmias, with prolongation of the QRS complex and QT interval being typical for TCA poisoning. In specialized laboratories, toxicological analyses can be performed to detect the specific active substance in blood or urine, but these tests are often not available in a timely manner in emergency situations.

Differential diagnosis includes other intoxications (e.g., with chocolate, xylitol, pesticides), neurological diseases, metabolic disorders, and primary cardiac diseases. A thorough anamnesis and the characteristic combination of symptoms are therefore crucial for a quick and correct diagnosis, which allows for timely initiation of specific therapy.

Therapeutic principles

During decontamination, the specific intoxication symptoms must be considered.
Vomiting should not be induced due to possible seizures and impaired swallowing reflex.
Activated charcoal and bowel cleansing with Glauber’s salt are indicated. Activated charcoal can also be administered several hours after ingestion and repeatedly at intervals.
Likewise, gastric lavage can still be helpful after 3–4 hours, as the intoxication is associated with a slowing of gastrointestinal transit.
In cases of (suspected) ingestion of larger quantities or sustained-release forms, endoscopic removal of tablets may also be possible.
There is no specific antidote, but physostigmine can treat the anticholinergic component in both dogs and cats. Sodium bicarbonate is very helpful in treating cardiac arrhythmias by correcting acidosis.
Lipid infusions are also indicated.
Otherwise, the therapy is symptomatic. As with all intoxications, stabilizing vital functions is paramount.
Vital functions, especially cardiovascular function, must be intensively monitored, and arrhythmias treated.
Renal function (diuresis) is stimulated, and confirmed urine output is controlled.
Simultaneously with infusion therapy to control renal function, acid-base balance disturbances, characterized by acidosis, can be treated with sodium bicarbonate.
Seizures must be medically interrupted.
Monitoring body temperature is also necessary.

Supplement

In antidepressant poisoning, rapid action is necessary:

Immediate Measures:

  • Induce vomiting (only within the first hour and only after consulting a veterinarian)
  • Administration of activated charcoal to reduce toxin absorption from the intestine (very effective for antidepressants)

Supportive therapy:

  • Infusion therapy (intravenous) for circulatory stabilization and accelerated toxin excretion
  • Control of neurological symptoms (benzodiazepines, e.g., diazepam for seizures and severe restlessness)
  • Cardiovascular stabilization: ECG monitoring, administration of antiarrhythmics (e.g., lidocaine for severe arrhythmias)
  • Temperature control (cooling for hyperthermia)
  • Sedation to control severe restlessness or neurological symptoms
  • Intensive monitoring of vital parameters required

Severe intoxications often require inpatient intensive care.

Prognosis & follow-up care

The prognosis is very good.

The prognosis for antidepressant poisoning depends significantly on various factors: the drug class and amount ingested, the time between ingestion and the start of treatment, and the animal’s general health status before poisoning. With early and adequate treatment, the prognosis is good to very good in most cases. The first 24–48 hours are critical, during which life-threatening complications such as severe cardiac arrhythmias, seizures, or respiratory paralysis can occur.

After surviving the acute poisoning phase, careful follow-up care is important. This includes control examinations to assess organ functions, especially heart, liver, and kidneys. A control ECG should be performed to detect possible persistent cardiac arrhythmias. For animals that showed severe neurological symptoms, a neurological follow-up examination is useful to identify possible residual damage.

Owners should be given detailed instructions on monitoring their pet at home. This includes recognizing warning signs such as renewed lethargy, coordination disorders, loss of appetite, or behavioral changes that may indicate delayed complications. Preventive measures to avoid new poisoning cases must be discussed, including the safe storage of medications in locked cabinets and the immediate disposal of spilled tablets.

Research outlook

Research in the toxicology of antidepressants in small animals is continuously evolving. Current studies focus on optimizing treatment protocols, especially for newer antidepressant classes. Lipid emulsion therapy, originally developed for treating local anesthetic poisoning, shows promising results in treating poisoning with lipophilic antidepressants and is increasingly being integrated into veterinary emergency protocols.

Molecular biological research approaches investigate genetic factors that influence sensitivity to antidepressants. Primarily, the MDR1 gene defect, which occurs in certain dog breeds like Collies, is a focus of research because it impairs the blood-brain barrier and can lead to increased toxicity of certain medications. Genetic tests could help identify particularly vulnerable animals in the future.

New antidotes and specific treatment approaches are being researched to improve the therapy for antidepressant poisoning. For example, specific serotonin antagonists are being investigated for treating serotonin syndrome in SSRI poisoning. The development of faster and more precise detection methods for antidepressants in biological samples could also improve diagnosis and treatment in the future.

Frequently asked questions (FAQs)

  1. Which antidepressants are most dangerous for pets?
    Tricyclic antidepressants like amitriptyline and imipramine are considered particularly toxic to dogs and cats, as they can cause severe cardiovascular and neurological symptoms even in small doses.
  2. How quickly do poisoning symptoms appear after antidepressant ingestion?
    The first symptoms can appear as early as 30 minutes to 3 hours after ingestion. However, with sustained-release preparations, the onset of symptoms may be delayed.
  3. Can my pet suffer permanent damage from antidepressant poisoning?
    With early and adequate treatment, the risk of permanent damage is low. However, severe intoxications can lead to lasting neurological or cardiac damage.
  4. May I induce vomiting in my pet if it has ingested antidepressants?
    Inducing vomiting should only be done after consulting a veterinarian, as there is a risk of seizures and aspiration pneumonia in antidepressant poisoning.
  5. Are antidepressants also used in veterinary medicine?
    Yes, certain antidepressants like clomipramine and fluoxetine are used in veterinary medicine to treat behavioral disorders, but in specially adapted dosages.
  6. Are certain pet breeds or species more susceptible to antidepressant poisoning?
    Dog breeds with the MDR1 gene defect (e.g., Collies) can be more sensitive to certain medications. Generally, smaller animals are at greater risk due to their lower body weight for the same amount ingested.
  7. What should I do if I suspect my pet has ingested antidepressants?
    Contact a veterinarian or veterinary emergency clinic immediately. If possible, note the name of the medication, the dosage, and the number of tablets potentially ingested.
  8. How long does my pet need to be monitored after antidepressant poisoning?
    Intensive veterinary monitoring is required for at least 24–48 hours, as delayed complications can occur.
  9. Can over-the-counter herbal antidepressants like St. John’s Wort also be dangerous for animals?
    Yes, even herbal preparations like St. John’s Wort can cause undesirable effects in animals, including increased photosensitivity and interactions with other medications.
  10. How can I prevent antidepressant poisoning in my pet?
    Store all medications in locked cabinets out of reach of pets. Make sure no tablets fall on the floor, and dispose of unneeded medications properly.

Literature

  • http://toxdocs.de/2018/intoxikationen-mit-trizyklischen-antidepressiva/
  • Löwe G, Löwe O. Emergencies in Dogs and Cats – A Veterinary Guide. 2nd Edition. Kreuztal: Kynos-Verlag. 2021; 208 pp.
  • Gwaltney-Brant, S. M. (2021). Antidepressant Toxicosis. In: Veterinary Toxicology: Basic and Clinical Principles. 3rd Edition. Academic Press, pp. 489-498.
  • Wismer, T. A. (2019). Antidepressant Poisoning in Small Animals. The Veterinary Clinics of North America: Small Animal Practice, 49(3), 567-581.
  • Fernandez, A. L., Lee, J. A., Rahilly, L., Hovda, L., Brutlag, A. G., & Engebretsen, K. (2022). The use of intravenous lipid emulsion therapy in veterinary toxicology. Journal of Veterinary Emergency and Critical Care, 32(1), 5-21.
  • Pöch, G., Dittrich, P., & Holzmann, S. (2020). Toxicology of antidepressants in small animals: clinical signs, diagnosis, and treatment. Journal of Veterinary Pharmacology and Therapeutics, 43(5), 385-395.
  • Kook, P. H., Quante, S., & Reusch, C. E. (2020). Pharmacological treatment of behavioral disorders in dogs and cats. The Veterinary Journal, 261, 105463.
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