Ketamine's Promise: A New Depression Treatment?

Ketamine is a psychedelic drug that has been used as an anesthetic in hospitals and veterinary clinics for decades. It is also known as a party drug that can cause an out-of-body experience. In recent years, ketamine has been explored as a potential treatment for severe, treatment-resistant depression (TRD) and has been found to rapidly alleviate symptoms in patients who have failed to respond to multiple other treatments. While ketamine is not a cure for depression, it has been shown to improve symptoms for a certain amount of time. However, there are concerns about the side effects of ketamine, including dissociation, intoxication, sedation, high blood pressure, and blurred vision. It is also important to note that ketamine has addictive properties and can cause harm when mixed with other drugs.

Ketamine's effectiveness in treating depression

Ketamine is a psychedelic drug with dissociative effects, which has been used as an anaesthetic in hospitals and veterinary clinics for decades. It has also gained notoriety as a recreational drug. In recent years, it has been explored as a potential treatment for severe, treatment-resistant depression (TRD) and has shown promising results.

Ketamine is thought to work by blocking NMDA receptors in the brain and interacting with the amino acid neurotransmitter glutamate. This process may lead to the regrowth of synapses (connections between neurons), effectively rewiring the brain. This is supported by studies on stressed mice, which showed improvements in behaviour and brain circuit function within three hours of being given ketamine, and regrowth of synapses 12 to 24 hours later.

Effectiveness in Treating Depression

Ketamine has been shown to be effective in treating TRD, particularly in cases where other treatments have failed to provide relief. It can rapidly reduce suicidality and relieve other serious symptoms of depression, with effects noticeable within 40 minutes to a few hours. This is in contrast to traditional antidepressants, which can take weeks or months to take effect.

The prescription version of ketamine, esketamine (brand name Spravato), is administered via a nasal spray and was approved by the FDA in 2019 for the treatment of hard-to-treat depression. Research has shown that ketamine nasal spray, in combination with regular antidepressants, can help people stay in stable remission for up to 16 weeks.

Side Effects and Considerations

While ketamine has shown effectiveness in treating TRD, it is not without its side effects and considerations. The main side effects include dissociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, nausea, and vomiting. It is also important to note that ketamine is not a cure for depression but rather improves symptoms for a certain amount of time. Additionally, there are concerns about the potential for repeated dosing to lead to decreased effectiveness and the need for larger doses over time.

Ketamine should be used with caution or avoided in certain groups, including individuals with a history of psychosis or schizophrenia, a history of substance use disorder, teenagers, pregnant or breastfeeding individuals, and older adults with dementia symptoms.

Ketamine has shown promising results as a treatment for severe, treatment-resistant depression, especially in cases where other treatments have failed. However, it is important to weigh the potential benefits against the side effects and considerations. More research is needed to fully understand the long-term benefits and risks of ketamine treatment.

Ketamine's side effects

Ketamine is a dissociative drug with a range of side effects, some of which can be serious. It is important to note that ketamine has addictive properties and is illegal for non-medical use.

Short-term side effects

When taken at relatively low doses, ketamine can cause:

• Disorientation, confusion, or loss of motor coordination
• Dizziness, nausea, or vomiting
• Increased blood pressure, heart rate, breathing, or body temperature
• Changes in sensory perceptions, including hallucinations
• Feeling detached from yourself, your surroundings, or your environment

Long-term side effects

The long-term effects of ketamine are not yet fully understood. However, regular, long-term use of ketamine may have the following side effects:

• Memory impairment
• Decline in executive functioning
• Cognitive and emotional changes
• Damage to the bladder, requiring surgical repair or even removal
• Urinary tract problems, including incontinence
• Abdominal pain
• Liver damage
• Flashbacks
• Problems with concentration
• Depression
• Psychotic symptoms such as hallucinations

Side effects of ketamine infusion

Ketamine is often given as an infusion into the bloodstream (intravenous or IV ketamine) to treat depression. This method of administration can cause:

• Perceptual disturbances (e.g. time appearing to speed up or slow down, blurry vision)
• Dissociation (out-of-body experiences)

Side effects of esketamine nasal spray

Esketamine (Spravato) is a nasal spray that has been approved by the FDA to treat depression. This form of ketamine may cause similar side effects to the infusion method, but the timing and intensity of those effects may differ.

Ketamine's use as a party drug

Ketamine is a potent medication used in anaesthetic medicine. It has been available for prescribed medical uses since the 1970s. It is also used as a pain medication and as a horse tranquilliser by vets. Ketamine is a popular party drug, especially among young people, and has been for the past two to three decades. It is relatively cheap and accessible, which has contributed to its popularity. It is also used as a date rape drug due to the dream-like state it induces in victims, making it difficult for them to move.

Ketamine is used for its 'dissociative' qualities, as it separates physical sensations from thoughts. It amplifies sensory reactions, intensifying the sounds of music and the experience of lights and atmosphere at parties, clubs, and raves. The vivid colours, bright lights, and calming sensations induce a trance-like feeling that is enticing for young party-goers. At higher levels, ketamine can produce effects similar to LSD, with users describing floating and flying sensations. This can lead to young people attempting dangerous stunts.

Ketamine creates a dream-like sensation, leaving teenagers and young adults feeling relaxed and chilled, often described as a feeling of inner peace. This feeling usually occurs close to an overdose and is often accompanied by nausea and confusion. Young people also describe feelings of being detached from reality, with altered abilities to recall time and place. The effects of ketamine usually begin around 15-20 minutes after ingestion and can last up to 2 hours.

Ketamine is psychologically addictive. Those who enjoy the sensations it induces are likely to want to use more of the drug and more frequently. This leads to an increased tolerance, requiring larger quantities to achieve the same high. Despite the negative consequences, young people continue to use ketamine, leading to addiction, permanent cognitive disability, memory loss, and permanent psychosis.

Ketamine can cause both short-term and long-term effects, even in infrequent users. It can cause havoc on the body's ability to regulate temperature, leading to sickness, vomiting, sweating, dehydration, seizures, increased blood pressure, difficulty breathing, and impaired body sensation or numbness. It can also cause brain changes leading to developmental issues and bladder problems.

Ketamine's use as an anaesthetic

Ketamine is a powerful general anaesthetic that has been in clinical use since 1970. It is a unique intravenous (IV) anaesthetic that produces a wide spectrum of pharmacological effects, including sedation, catalepsy, somatic analgesia, bronchodilation, and sympathetic nervous system stimulation.

Ketamine is highly lipid-soluble and undergoes rapid breakdown and redistribution to peripheral tissues. It is metabolised extensively in the liver and has a cumulative effect, with gradual resistance building up on repeated administration. It stimulates the cardiovascular system, resulting in an increase in heart rate, blood pressure, and cardiac output. It has minimal effects on central respiratory drive and produces airway relaxation by acting on various receptors and inflammatory cascades in the bronchial smooth muscles.

Ketamine has a dissociative effect, where the patient appears awake but is detached from their surroundings with their eyes remaining open. It can be used as an IV induction agent in emergency settings for shocked or hypotensive patients and is considered the induction agent of choice for patients with active bronchospasm. It is also the drug of choice for patients with congenital heart disease with right-to-left shunt due to its beneficial cardiovascular effects.

Ketamine is widely used for burn dressing changes, during excision and grafting, and for sedation. It is also used for premedication, either orally, intranasally, intramuscularly, or intravenously, and as an adjunct to caudal blocks, IV regional anaesthesia, peripheral nerve blocks, and stellate ganglion blocks. It is effective in preventing post-anaesthesia shivering and is used for procedural sedation for adults and children in emergency departments.

Ketamine is also used for sedation and analgesia in critical care units, co-induction and total IV anaesthesia, and acute and chronic pain management. It has been found to be effective in treating refractory status epilepticus and has shown promising results in treating depression and social anxiety disorder.

However, it is important to note that ketamine has its limitations and potential side effects. It is not suitable for patients with hypertension, schizophrenia, or raised intraocular pressure. It can cause an increase in salivation, which may be troublesome and lead to laryngospasm in children. Ketamine also produces dose-dependent psychological manifestations, such as emergence reactions, dreams, hallucinations, and long-term psychotomimetic effects. It has the potential for addiction and can cause ulcerative cystitis, secondary renal damage, and hepatic failure when used in high doses.

Ketamine's availability at outpatient clinics

Ketamine is a medication that is increasingly being used to treat some cases of major depression. It was initially used as an anesthetic on battlefields and in operating rooms. The medication is particularly promising for its ability to rapidly reduce suicidality and relieve other serious symptoms of depression.

In the United States, there are now hundreds of ketamine clinics offering the drug as an off-label treatment for a wide variety of mental health problems. The treatment is not covered by insurance and can cost patients from $400 to $800 per session on average.

Ketamine clinics are largely unregulated, and there are concerns about the lack of standardisation of treatment protocols and the qualifications of staff. While it is legal for doctors to prescribe ketamine, the FDA has not approved it for mental health treatment, meaning that individual practitioners develop their own treatment protocols. Some clinics are staffed by anesthesiologists or psychiatrists, while others may not have mental health professionals on staff at all.

There are also concerns about the potential side effects of ketamine, which can include changes in mood and blood pressure, as well as nausea and drowsiness. In addition, ketamine has addictive properties, and there is a risk of patients experiencing a "bad trip" or "k-hole", a terrifying and disorienting experience.

Despite these concerns, many patients report that ketamine infusions have been lifesaving, providing immediate improvement for severe depression. For some, ketamine has been a lifeline when other treatments have failed. However, it is not a cure-all, and it does not work for everyone.

Overall, while ketamine may be a promising treatment for depression, the lack of regulation and standardisation in the industry means that patients seeking treatment at ketamine clinics should proceed with caution and ensure that they are fully informed about the potential risks and benefits.

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