Trazodone

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Trazodone

Common Trade Names: Desyrel, Desyrel Dividose, Oleptro, and Trazodone D.

Other Names: 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one

While it is not considered a dependency-forming substance, individuals who have struggled with substance use disorder in the past are at risk for developing psychological dependence on trazodone, especially if it is used in conjunction with other substances. If you know someone who struggles with trazodone use disorder, read on to learn how you can help them recover.

A Brief History of Trazodone

Trazodone is a prescription medication primarily used in the treatment of major depressive disorder, panic and anxiety disorder, and insomnia. Trazodone was first synthesized in Italy in the 1960s. It was offered to the medical community soon after, but because of its unfavorable side effects – including loss of consciousness, dizziness, priapism, and cardiac arrhythmias – trazodone did not become widely accepted as an antidepressant. After several clinical trials, physicians began recognizing its benefits in treating major depressive disorder. In 1981, trazodone, under the brand name Desyrel, was officially approved by the FDA for the treatment of depression. Today, trazodone is sold under several trade names such as Oleptro, which is a prescription medication used as an adjunct therapy for sleep disorders such as insomnia as well as anxiety and panic disorders.

How Does Trazodone Work in the Human Body?

Trazodone belongs to the drug class called SARIs (serotonin antagonist and reuptake inhibitors), together with other drugs such as phenylpiperazine and mepiprazole. It is primarily used as an antidepressant but is also generally used as an anxiolytic and hypnotic. Trazodone works by blocking the serotonin 5-HT2 receptors and functionally inhibiting reuptake of serotonin, thereby increasing the amount of active serotonin in the circulation.

As mentioned, trazodone is FDA-approved for patients with major depressive disorders, either as a monotherapy or in combination with other drugs or behavioral and psychosocial interventions. Studies have shown that trazodone has similar efficacy with other antidepressants like tricyclic antidepressants and selective serotonin reuptake inhibitors(SSRIs), but with better tolerance and lower abuse potential. In addition, adverse effects typically associated with SSRIs and SNRIs, such as insomnia, anxiety, and sexual dysfunction, are not seen in trazodone therapy.

Off-label uses of trazodone include sleep disturbances, anxiety and panic disorders, Alzheimer’s disease, substance abuse, fibromyalgia, and bulimia. Trazodone may also be prescribed for patients with post-traumatic stress disorder, if initial therapy with SSRIs are found to be ineffective. Clinical studies have demonstrated that trazodone dosage of 50-200mg is useful in decreasing nightmare episodes and improving sleep among PTSD patients. Trazodone has also shown to improve apnea and hypopnea episodes in patients suffering from obstructive sleep apnea by raising the respiratory threshold and decreasing the risk of respiratory instability.

How Is Trazodone Taken or Administered?

Trazodone comes in 50mg, 100mg, 150mg, and 300mg tablets. It also has extended-release formulations available in 150mg and 300mg tablets. Oral drops and injection solutions are also available in some cases. Oral intake of trazodone must be scheduled preferably after meals to reduce the risk for lightheadedness and postural hypotension.

The recommended dose of trazodone when indicated for depression is 150mg once a day. The dose may be increased by 50mg every three days, up to 300mg per day. For inpatients, the dose may be increased to up to 600mg every day.

The recommended dose of trazodone in patients suffering from insomnia secondary to depressive disorder is 50 to 100mg every day. Studies have shown that 100mg dosage is the most effective in reducing sleep disturbances.

In the elderly, trazodone intake must not exceed 100mg per day.

What Are the Immediate and Long-Term Effects of Trazodone Use?

Trazodone generally has a favorable safety profile. However, misuse of trazodone can still occur and may be associated with a wide range of adverse effects including:

  • Headache
  • Dizziness and drowsiness
  • Fatigue
  • Orthostatic hypotension
  • Visual hallucinations

Because of trazodone’s interaction with hERG potassium channels, it may also lead to:

  • QT prolongation
  • Arrhythmias

Trazodone also carries mild anticholinergic properties, hence trazodone toxicity may cause some anticholinergic effects such as:

  • Dry mouth
  • Urinary retention
  • Constipation
  • Decreased sweating

In general, antidepressants such as trazodone are associated with an increased incidence of suicidal ideation especially among adolescents and young adults. Trazodone has also been shown to cause priapism, which is a persistent and painful penile erection and can lead to neurological damage when left untreated. Male patients under trazodone therapy are advised to seek immediate medical attention if there is suspicion of priapism.

In rare cases, long-term use of trazodone may also be associated with transient elevations in liver enzymes and can be implicated in symptomatic acute liver injury.

Signs of Trazodone Use Disorder

Trazodone has a very low abuse potential and is not considered an addictive or habit-forming drug. However, due to its sedative and hypnotic properties, misuse of trazodone can still occur in rare cases. Close observation of patients, particularly those who have a history of substance abuse, must be considered in order to prevent progression to trazodone use disorder.

There are four main categories for behaviors in the 5th Edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) that are related to substance use disorder, including misuse of trazodone:

  1. Impaired control
  2. Social impairment
  3. Risky use
  4. Pharmacological indicators (tolerance and withdrawal)

Each of the 11 criteria for substance use disorder falls into one of these categories:

Impaired control

  1. Taking more trazodone than prescribed, or continuing to take it beyond its prescribed period
  2. Being unable to reduce or stop the use of trazodone
  3. Exerting effort and spending time acquiring more trazodone
  4. Cravings for trazodone that may be uncontrollable

Social impairment

  1. Failing to fulfill work, school, or family obligations due to trazodone use
  2. Using trazodone despite encountering conflicts in relationship because of it
  3. Loss of interest in professional, social, or recreational activities because of trazodone use

Risky Use

  1. Using trazodone in potentially hazardous situations including operating heavy machinery or driving a car
  2. Continuing to use trazodone even after physical or psychological problems begin to appear

Physical tolerance

  1. Needing more trazodone to get the effect desired, also known as tolerance
  2. Development of painful and uncomfortable withdrawal symptoms

Symptoms associated with trazodone withdrawal include:

  • Intense mood swings
  • Agitation and confusion
  • Muscle pain
  • Fatigue
  • Insomnia
  • Dizziness
  • Increased sweating

Rehab and Treatment for Trazodone Use Disorder

The process of rehab and treatment for abuse of most drugs, including abuse of trazodone, generally follows a similar pattern. Treatment begins by assisting the patient through detoxification, a process that aims to cleanse the body of the abused substance and prevent the development of withdrawal symptoms that may negatively affect their treatment journey.

There are two approaches to detoxification: medical and non-medical. Medical detoxification uses pharmacologic interventions to help the patient wean off the abused substance and reverse its actions on the body. As of today, there are no FDA-approved medications that could aid in the detox of trazodone abusers. For cases like this, a widely accepted approach is to slowly taper off the doses that the patient takes or replace the abused substance with an alternative drug that has a similar safety profile and efficacy but with much lower abuse potential. Patients are never encouraged to abruptly stop taking the abused substance as it can lead to severe, or even fatal withdrawal symptoms.

On the other hand, non-medical detox involves the use of various psychosocial and behavioral strategies to help the patient wean off the drug, prevent relapse episodes, and ultimately, achieve a drug-free state. Like the medical approach, this strategy must be done under the supervision of rehab professionals.

Other strategies include psychotherapy, counselling, and outpatient treatment.

Psychotherapy. The most commonly used forms of psychotherapy in drug rehab are cognitive-behavioral therapy (CBT) and psychodynamic therapy. Relapse prevention, aversion therapy, and contingency contracting are some of the interventions under CBT. These interventions aim to identify maladaptive and destructive behavioral patterns that increase an individual’s risk for drug abuse and discover healthier habits to help them reduce and cope with these behaviors.

Psychodynamic therapy, on the other hand, allows an individual to deepen their self-awareness and awareness of their inner conflicts and motivations. The goal of psychodynamic therapy is self-correcting behavior, through which an individual will be able to make better choices for themselves through a deep sense of self-awareness.

Counselling. Much like psychotherapy, the goal of counselling is to achieve a drug-free state for the client by providing emotional support, encouraging abstinence, and identifying possible roadblocks in their treatment journey. Counselling can be done either by a licensed professional or by former drug abusers who have already achieved full recovery.

Outpatient treatment. Outpatient treatment involves the use of strategies mentioned above, either as monotherapy or in various combinations. Outpatient treatment allows an individual to complete their rehab process without disrupting their day-to-day activities. This option is preferable for patients with relatively milder symptoms, less severe addiction issues, and those whose commitment to the treatment process can be guaranteed.

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