Duloxetine

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Duloxetine

Common Trade Names: Cymbalta, Irenka, Drizalma Sprinkle

Other Names: (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine

Duloxetine is an antidepressant medication whose efficacy in the treatment of major depressive disorder has long been well-established. While duloxetine has a lot of therapeutic benefits, it also carries a risk for addiction, especially when misused. Read on to know more about duloxetine abuse and its treatment.

A Brief History of Duloxetine

Duloxetine was synthesized and developed by researchers from Eli Lilly and Company. The drug was patented in 1990. It was approved by the US Food and Drug Administration (FDA) for depression and diabetic neuropathy in 2004. In the same year, the European Union also approved duloxetine for use in the treatment of stress urinary incontinence (SUI).

Eli Lilly and Company also sought US FDA approval for use of duloxetine in SUI. However, after several discussions with the agency, Eli Lilly eventually withdrew its application, stating that “the agency is not prepared at this time to grant approval.”

In 2007, the US FDA approved duloxetine for the treatment of generalized anxiety disorder (GAD). In the same year, duloxetine was also granted approval by Health Canada for the treatment of depression and diabetic peripheral neuropathic pain.

How Does Duloxetine Work in the Human Body?

Duloxetine is an antidepressant medication belonging to the drug class called serotonin and norepinephrine reuptake inhibitors (SNRIs). Duloxetine works by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine, leading to increased concentrations in the central nervous system. Duloxetine has also been found to increase dopamine levels within the prefrontal cortex by inhibiting norepinephrine transporters.

Duloxetine also has analgesic properties which are brought about by its ability to enhance the activity of both noradrenergic and serotonergic neurons. These neurons inhibit the activity of dorsal horn neurons which are partially responsible for the perception of pain along the descending spinal pathway. Thus, suppression of dorsal horn neurons can result in diminished pain sensation.

As mentioned above, duloxetine has been FDA-approved for the treatment of major depressive disorder and diabetic peripheral neuropathy. Other FDA-indicated uses of duloxetine include general anxiety disorder (GAD), fibromyalgia, and chronic musculoskeletal pain, especially osteoarthritis of the knee and low back pain. Off-label uses of duloxetine include SUI and chemotherapy-induced peripheral neuropathy.

There are several contraindications to the use of duloxetine. First, duloxetine is contraindicated in patients who have shown allergic or hypersensitivity reactions to it or any of its components. Second, duloxetine is also contraindicated in patients who recently took (i.e. within two weeks) or are currently taking monoamine oxidase inhibitors (MAOIs) such as isocarboxazid and selegiline. Third, patients with severe renal dysfunction or acute-angle glaucoma must not take duloxetine. Lastly, duloxetine must not be taken by patients who are also currently taking linezolid or IV methylene blue, as their combination leads to an increased risk for serotonin syndrome.

How is Duloxetine Taken or Administered?

Duloxetine is available in 20mg, 30mg, 40mg, and 60mg delayed-release capsules. It can be taken with or without meals but must be swallowed whole and should not be chewed or crushed.

The following are the recommended doses of duloxetine in various conditions:

Major Depressive Disorder

Initial: 40-60mg per day, not to exceed 120mg per day; may also be given initially at 30mg per day in some patients to allow them to adjust to medication

Maintenance: 60mg per day

Diabetic peripheral neuropathic pain

Initial: 60mg per day; lower starting dosage if there are concerns regarding tolerability, not to exceed 60mg per day

Generalized Anxiety Disorder

Initial: 60mg per day; may also be given initially at 30mg per day if there are concerns regarding tolerability, and increased up to 60mg per day after one week

Fibromyalgia (Cymbalta only)

Initial: 30mg per day, and may be increased up to 60mg per day after one week

Titration approach: Starting dose of 20mg per day; increase the dose by 20mg every week, not to exceed 60mg per day

Chronic musculoskeletal pain (including osteoarthritis of the knee and low back pain)

Initial: 30mg per day, may be increased up to 60mg per day after one week; not to exceed 60mg per day

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

Just like other antidepressants, duloxetine is associated with increased suicidal ideation particularly among adolescents and young adults. Other adverse effects of duloxetine include:

  • Headache
  • Drowsiness
  • Nausea
  • Abdominal pain
  • Decreased appetite
  • Weakness or fatigue
  • Dry mouth
  • Weight loss
  • Dizziness
  • Insomnia
  • Increased sweating
  • Diarrhea or constipation
  • Tremor
  • Erectile dysfunction

Duloxetine can also lead to serious and potentially life-threatening conditions, such as:

  • Serotonin syndrome
  • Syncope
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
  • Mania
  • Hepatotoxicity

Signs of Duloxetine Use Disorder

The Diagnostic and Statistical Manual (DSM) 5th Edition identified four broad aspects of behaviors which have been linked to substance use disorders (SUDs), including abuse of duloxetine:

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

Under these categories, there are 11 criteria necessary for the diagnosis of SUDs:

Impaired Control

  1. Misusing the substance by taking more doses or for a longer period of time than was prescribed
  2. Being unable to successfully stop from or cut back on substance use despite multiple attempts
  3. Spending a lot of time getting or recovering from use of the substance
  4. Craving for the substance all the time

Social Impairment

  1. Substance use disables the individual from fulfilling personal obligations
  2. Substance use causes relationship or interpersonal problems
  3. Substance use makes the patient miss important personal and social activities

Risky Use

  1. Continued use of the substance despite being in the middle of potentially dangerous situations such as while driving a car or operating heavy machinery
  2. Continued use of the substance despite exacerbation of physical and psychological problems

Physical Tolerance

  1. The individual feels the need to increase the amount of substance taken to achieve the desired effects (tolerance)
  2. The individual develops withdrawal symptoms after abrupt cessation of substance use (withdrawal)

Rehab and Treatment for Duloxetine Use Disorder

In general, duloxetine is considered a non-addictive and non-habit-forming antidepressant medication. Clinical trials on duloxetine have not demonstrated risky, drug-seeking behavior among its participants. Nevertheless, physicians are still encouraged to carefully evaluate and monitor patients, particularly those with a history of substance abuse, as they are at an increased risk for developing duloxetine use disorder.

Currently, no specific medication has been FDA-approved for the treatment of duloxetine abuse. However, there are several strategies that can be utilized to help patients overcome their addiction to duloxetine.

One of the first and most important strategies in the rehab and treatment of duloxetine use disorder is detoxification or detox. In the detox process, patients are weaned off duloxetine in order to cleanse the body of the residual substances that have accumulated from long-term misuse. This must be done under the guidance of a rehab professional, as abrupt cessation of duloxetine use can lead to several withdrawal symptoms that can be life-threatening.

Gradual tapering of doses over several weeks seems to be an effective approach for most detox processes, including that for duloxetine addiction. While there is no absolute rate of dose tapering recommended for duloxetine, the general principle is slow discontinuation and regular monitoring of the patient in order to prevent development of withdrawal symptoms.

There are also several behavioral and psychosocial interventions that may be instituted to encourage abstinence among duloxetine abusers. Some examples are counselling and psychotherapy.

Counselling

The role of counselling in the rehab process is well-evidenced. Counselling aims to provide patients with strong social and emotional support as they undergo rehab. Counsellors can also help patients identify possible roadblocks that can slow down or hinder their treatment process and come up with healthy workarounds to overcome these barriers.

Psychotherapy

Cognitive-behavioral therapy (CBT) and psychodynamic therapy are the most common forms of psychotherapy used in the rehab process. CBT includes programs such as contingency contracting, relapse prevention, and aversion therapy. The goal of CBT is to identify destructive behavioral patterns that lead to addiction and teach patients how to cope with these behaviors properly.

The general principle of psychodynamic therapy, on the other hand, is self-correction. In psychodynamic therapy, patients are taught how to look deeply into themselves and enhance their sense of self-awareness. The goal of these techniques is to encourage the patients to make better choices as they learn more about themselves.

Get the Help You Need

The key to a successful recovery from addiction is early intervention. Better Addiction Care offers excellent rehab referral services to anyone who might be suffering from duloxetine abuse. Do not hesitate to ask for help. Call our hotline or submit a contact form to get started.

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