Treatment for depression: Duloxetine (CymbaltaⓇ) and amitriptyline, what are they?

Antidepressants

The pharmaceutical class of antidepressants is divided into several categories: 

• Selective serotonin reuptake inhibitors (SSRIs), 
• Serotonin–norepinephrine reuptake inhibitors (SNRIs), 
• Tricyclic antidepressants (TCAs), 
• Monoamine oxidase inhibitors (MAOIs) 
• Atypical antidepressants. 

Physiopathologically, depression is characterized by a deficit in certain neurotransmitters (serotonin, noradrenaline and dopamine). These allow the neurons to communicate with one another. 

Antidepressants therefore aim to increase the concentration of neurotransmitters. 

These drugs are effective in about 70% of cases. Additionally, it takes from 2 to 4 weeks from initial intake for the antidepressants to take effect. It should be noted as well that a number of adverse side effects can be felt from the start of treatment, which can lead some patients to stop their treatment prematurely.

In addition, fast-acting anxiolytics can be prescribed during this period to support the patient during this waiting period as a complement (benzodiazepines for example). However, anxiolytics are not a cure for depression. They simply alleviate certain symptoms such as sleep disorders and anxiety. They are generally not prescribed for more than 4 weeks (due to the risk of dependence). If the depression is complicated by persistent anxiety disorders, an antidepressant with anxiolytic activity may be prescribed. 

A second reason for prescribing antipsychotics at the beginning of treatment is the release of motor inhibition. Indeed, when taking antidepressants, during the first days or weeks of treatment (when the beneficial effect is not yet present), the patient may experience anxiety (or an aggravation of pre-existing anxiety). In addition, the lifting of motor inhibition (inhibition due to depression) will occur more quickly than the reversal of mood. For this reason, the risk of suicide increases, especially in patients who already have it or who have dark thoughts.

Furthermore, antidepressant treatment often exceeds 6 months in order to strengthen recovery. To prevent any risk of relapse, even if the patient no longer feels the effects of the depression, the duration of the treatment must be respected. The treatment should be stopped gradually by lowering the doses little by little until it is stopped completely.

On the other hand, all antidepressants are can trigger manic episodes (indicative of bipolar disorder) in individuals with a predisposition. Therefore, in case of euphoria, unusual excitement or abnormal behavior, it is important to seek medical care. 

We will now look into two drugs in more detail: duloxetine (CymbaltaⓇ) and amitriptyline.

Duloxetine (CymbaltaⓇ)

Duloxetine, often marketed internationally as CymbaltaⓇ, is a serotonin–norepinephrine reuptake inhibitors (SNRI). Duloxetine prevents the reuptake of serotonin and norepinephrine in the central nervous system and therefore increases the level of these two neurotransmitters.

In addition to its antidepressant action, this drug is also used as an anxiolytic in cases of generalized anxiety and as an analgesic (painkiller) in the treatment of neuropathic pain in people living with diabetes.

Side effects and contraindications (non exhaustive)

Duloxetine can be used for several indications. Yet, whatever the use, it is important to be aware of its side effects and contraindications.

The most common side effects observed with CymbaltaⓇ are:

• Digestive effects (nausea),
• Anticholinergic effects (dry mouth, constipation),
• Sedation,
• Dizziness,
• Headache,
• Excessive sweating,
• Weight loss.

In 1 to 10% of cases, the following effects have been observed:

• Sexual disorders,
• Vomiting,
• Abnormal dreams,
• Tinnitus,
• Blurred vision.

Finally, in less than 1% of cases, patients have experienced hallucinations, taste disorders, weight gain, increased blood sugar levels, nosebleeds and high blood pressure.

Indeed, duloxetine is contraindicated in patients with uncontrolled hypertension. Due to the increase in norepinephrine, in rare cases, patients may experience hypertensive crises (which is more common in patients with pre-existing hypertension). Therefore, blood pressure monitoring is recommended in in patients with high blood pressure and/or heart disease, especially during the first month of treatment. Dose adjustment or discontinuation of duloxetine should be considered in patients with persistent increases in blood pressure.

Patients taking anticoagulants or antiplatelet drugs or who are prone to bleeding should be cautious when using this drug due to the risk of bleeding.

In addition, dosage adjustments should be made in patients with mild-to-moderate renal failure. Duloxetine is contraindicated for patients undergoing dialysis for severe renal failure (due to the increased concentration of the drug in the plasma).

Furthermore, the combination of CymbaltaⓇ with products containing St John's wort may increase the frequency of adverse reactions. 

Finally, as with any psychoactive drug, it is advisable to avoid association with alcohol or other products affecting the central nervous system (it can cause an increased risk of drowsiness), although no clear interaction has been observed.

Drug interactions (non exhaustive)

MAOIs, particularly irreversible, non-selective MAOIs (Iproniazid), have the potential to interact with duloxetine. Indeed, the combination of these two treatments may cause serotonin syndrome (altered mental state, tachycardia, hypertension, diarrhea, hyperthermia, tremors and chills).

In addition, any combination with other serotonergic agents (such as other antidepressants) should be avoided. In rare cases, serotonin syndrome have been described. This type of syndrome may require hospitalization or even cause death.  

Patient opinions

According to the Carenity UK fact sheet for duloxetine, 10 Carenity members have shared their opinion. They rated its effectiveness at around 70%. 

Almost 50% (46%) of members have reported experiencing significant side effects (mainly sweating, weight gain and digestive problems).   

Amitriptyline (formerly marketed as Elavil^Ⓡ and Endep^Ⓡ)

Amitriptyline, formerly marketed as ElavilⓇ and EndepⓇ and commonly dispensed as a generic, is also an antidepressant. It is part of the tricyclic antidepressants (TCA) class.

As with duloxetine, the use of amitriptyline is not limited to depression. It is also used in adults for the treatment of neuropathic pain, migraine and other related headaches and shingles.

In children over the age of 6, amitriptyline can also be used for bed-wetting.

Side effects and contraindications (non exhaustive)

The adverse effects of tricyclic antidepressants are caused by their mechanism of action. Indeed, they are responsible for peripheral (dry mouth, urinary retention, constipation, tachycardia) and central (tremors, memory disorders, confusion and convulsions in susceptible individuals, such as people with epilepsy or alcoholics) anticholinergic effects. Erectile dysfunction and dizziness have also been observed.

Sedation and weight gain have also been described in some patients.

Furthermore, TCAs are contraindicated in cases of benign prostate enlargement (BPE), benign prostatic hyperplasia (BPH), angle-closure glaucoma or heart disease (due to hypotensive, tachycardia and arrhythmic effects). Because of the latter contraindication, an electrocardiogram is recommended before the introduction of the treatment.

Drug interactions (non exhaustive)

This class of drugs should not be used in combination with MAOI antidepressants (risk of serotonin syndrome) or sultopride (an antipsychotic) because of the increased risk of cardiac arrhythmia. 

As with duloxetine, association with alcohol or other products acting on the central nervous system is contraindicated. These include benzodiazepines, hypnotics and some morphine drugs.

Patient opinions

12 members have shared their opinion on the Carenity UK amitriptyline fact sheet. 54% of members have deemed this treatment effective and 50% of members have experienced side effects, notably dry mouth.  

Conclusion 

Though these two antidepressants belong to two different drug classes, they share a number of common characteristics. They both act on neurotransmitters and therefore produce a positive change in mood (there is no effect on the mood of a subject not affected by depression).

Because of their action, these drugs have many drug interactions and side effects. Therefore, before taking any other treatment, it is recommended to inform your doctor, pharmacist and dentist (due to a possible interaction with local anesthetics) of your antidepressant treatment.  

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