Zoloft vs Cymbalta

Listen to the article instead of reading through it.


Zoloft and Cymbalta are two such drugs that are often prescribed for major depressive disorder (MDD) or other types of depression. These medications alter the concentrations of compounds in the brain, known as neurotransmitters, to help stabilize patients' moods and manage their symptoms. Zoloft is classified as a selective serotonin reuptake inhibitor (SSRI), primarily affecting levels of serotonin in the brain. In contrast, Cymbalta is known as a serotonin-norepinephrine reuptake inhibitor (SNRI), which means it affects both serotonin and norepinephrine levels. Though they work on different neurotransmitters, both these drugs aim at achieving mood stabilization in individuals suffering from depression.

What is Zoloft?

Sertraline (the generic name for Zoloft) is an SSRI antidepressant, similar to Prozac. It was first approved by the FDA in 1991. This drug works by increasing levels of serotonin in the brain due to inhibition of its reuptake, essentially prolonging its availability and effect on postsynaptic receptor sites. Zoloft is prescribed for a variety of conditions including different forms of depression, panic attacks, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder and even premenstrual dysphoric disorder.

On the other hand, Duloxetine (Cymbalta's generic name) falls under a newer category called SNRIs or serotonin-norepinephrine reuptake inhibitors and was approved by FDA in 2004. Cymbalta works similarly to Zoloft but it also increases norepinephrine levels along with serotonin which can lead to higher efficacy but also more side-effects compared with SSRIs like Zoloft due to increased neurotransmitter activity overall.

The decision between these two drugs often comes down to individual patient response and tolerance as well as symptomatology since although both are used for depression treatment they may have divergent effects upon comorbid symptoms such as pain syndromes where Cymbalta has shown some advantages.

What conditions is Zoloft approved to treat?

Zoloft is approved for the treatment of various mental health conditions:

  • Major depressive disorder (MDD)
  • Obsessive-compulsive disorder (OCD)
  • Panic disorder
  • Post-traumatic stress disorder (PTSD)
  • Social anxiety disorder
  • Premenstrual dysphoric disorder

On the other hand, Cymbalta is indicated for several different medical conditions that include not only mental health disorders but also certain types of chronic pain:

  • Generalized Anxiety Disorder (GAD)
  • Major Depressive Disorder (MDD)
  • Diabetic Peripheral Neuropathic Pain
  • Fibromyalgia
  • Chronic Musculoskeletal Pain.

How does Zoloft help with these illnesses?

Zoloft is effective in managing depression by enhancing the concentration of serotonin in the brain's synapses. It accomplishes this by inhibiting its reuptake into neurons, thus maintaining higher levels for extended periods. Serotonin, a neurotransmitter that acts as a communication medium within the brain and body at large, critically impacts mood, cognition, memory, sleep regulation, appetite and other physiological functions. Lower levels of serotonin are believed to be present in individuals with depression. By increasing serotonin concentrations therefore, Zoloft can alleviate depressive symptoms and aid patients in managing their condition while stabilizing their mood.

In contrast to Zoloft which primarily targets serotonin receptors only (SSRI), Cymbalta employs a dual approach by inhibiting the reuptake of both serotonin and norepinephrine; two neurotransmitters implicated in regulating mood amongst other crucial bodily processes. Consequently it’s known as an SNRI antidepressant medication instead of an SSRI like Zoloft. This additional action on norepinephrine could potentially make Cymbalta more effective or preferred over SSRIs for certain types of depression or anxiety disorders where deficits or imbalances between these two key neurotransmitters may exist.

What is Cymbalta?

Cymbalta, also known by its generic name duloxetine, is a serotonin-norepinephrine reuptake inhibitor (SNRI). This means that it increases the levels of serotonin and norepinephrine in the brain by reducing their reabsorption. Cymbalta also has some effect on pain signaling in the nervous system and can be used to treat chronic pain conditions such as fibromyalgia. It was first approved by the FDA in 2004. Unlike Zoloft, which is an SSRI antidepressant, Cymbalta does not solely focus on inhibiting serotonin reuptake but also impacts norepinephrine levels which can help with certain types of depressive disorders where imbalance of these two key neurotransmitters exists. Therefore, its side-effect profile is somewhat different than that of SSRIs like Zoloft - while it may still cause nausea or sexual dysfunction (common side effects with many antidepressants), its dual action mechanism could lead to a broader range of potential benefits for patients who do not respond well to "typical" SSRI depression medications like Zoloft.

What conditions is Cymbalta approved to treat?

Cymbalta is licensed for treatment of various conditions and disorders, including:

  • Major depressive disorder (MDD)
  • Generalized anxiety disorder (GAD)
  • Diabetic peripheral neuropathic pain
  • Fibromyalgia
  • Chronic musculoskeletal pain

How does Cymbalta help with these illnesses?

Serotonin and norepinephrine are neurotransmitters that play crucial roles in mood regulation, alertness, focus, and stress response. Low levels of these neurotransmitters have been linked to depression. Cymbalta works by increasing the levels of serotonin and norepinephrine available in the brain, thereby alleviating some of the symptoms associated with clinical depression or generalized anxiety disorder. Unlike Zoloft which predominantly affects serotonin levels, Cymbalta’s dual-action on both serotonin and norepinephrine can make it a more suitable option for patients who do not respond well to typical SSRIs like Zoloft or may be combined with other antidepressants when necessary for amplified effect.

How effective are both Zoloft and Cymbalta?

Both sertraline (Zoloft) and duloxetine (Cymbalta) are widely used in managing various psychiatric disorders, including depression and anxiety. They were initially approved by the FDA within a decade of each other, with Zoloft being introduced in 1991 and Cymbalta following in 2004. As they act on different neurotransmitters - Zoloft primarily affects serotonin, while Cymbalta impacts both serotonin and norepinephrine - they might be prescribed under differing circumstances.

A head-to-head study conducted in 2007 demonstrated that both drugs exhibited similar efficacy when it comes to treating depressive symptoms. However, due to its dual action on two neurotransmitters, duloxetine may have an edge over sertraline for individuals who don't respond adequately to selective serotonin reuptake inhibitors alone.

A comprehensive review from 2016 reported that sertraline is effective at reducing depressive symptoms starting from the first few weeks of treatment. Its side effect profile is relatively mild compared to many older antidepressants, making it well-tolerated among diverse populations – including older adults and pregnant women.

Duloxetine has been shown through meta-analyses to be more effective than placebo at treating depression as well as certain types of chronic pain due to its norepinephrine component. Though considered a second-line treatment option after SSRIs like sertraline fail or aren't tolerated well by patients, evidence supports Duloxetine's effectiveness as a stand-alone treatment for depression as well as part of combination therapy approach. Moreover, because of its unique pharmacology affecting two key neurotransmitters involved in mood regulation and pain perception simultaneously, Duloxetine could be optimal for patients who either did not respond well solely to SSRIs or those needing relief from neuropathic pain associated with conditions such as fibromyalgia or diabetic peripheral neuropathy.

abstract image of a researcher studying a bottle of drug.

At what dose is Zoloft typically prescribed?

Oral dosages of Zoloft can range from 50 to 200 mg/day, but studies have suggested that a starting dose of 50 mg/day is typically sufficient for treating major depressive disorder in most adults. Adolescents and elderly individuals may be started on lower doses, such as 25 mg/day. In either population, the dosage can be gradually increased after one week if there's no adequate response. The maximum dosage should not exceed 200 mg/day under any circumstances. Comparatively, Cymbalta has a typical starting dose of 60mg once daily for depression in adults which may increase over time depending on your doctor's advice, but it should not exceed the maximum recommended dose of 120mg per day.

At what dose is Cymbalta typically prescribed?

Cymbalta treatment is typically initiated at a dose of 30 to 60 mg/day. The dosage can then be increased, if necessary, up to a maximum of 120 mg/day divided into two doses, spaced approximately 12 hours apart. It's important to note that this higher dose may be explored if there is no response or insufficient response to therapy at the initial dosage after several weeks. As always in medical treatments, it's advisable for patients not to adjust their dosages without consulting with their healthcare provider first.

What are the most common side effects for Zoloft?

Common side effects of Zoloft (sertraline) and Cymbalta (duloxetine) can include:

  • Anxiety
  • Insomnia or sleepiness/drowsiness
  • General weakness and fatigue
  • Tremor or shaking sensations
  • Changes in appetite, possibly leading to weight changes
  • Nausea, indigestion (discomfort in the upper stomach), or diarrhea
  • Dry mouth
  • Decreased libido (sex drive)
  • Difficulty with ejaculation/orgasm
  • Sweating more than usual
  • Abnormal dreams
    -Influenza-like symptoms such as fever, chills, body aches etc. -Sore throat or inflammation of sinuses.

Always consult your doctor if you experience any of these side effects while taking either medication.

abstract image of a patient experiencing side effect

Are there any potential serious side effects for Zoloft?

While Cymbalta and Zoloft are both used to treat depression, anxiety, and certain other conditions, they can have different side effects. It's important to know that these medications may increase the risk of suicidal thoughts or actions in some people, especially those under 24 years old.

Severe allergic reactions are rare but possible with both drugs. If you notice symptoms such as hives; difficulty breathing; swelling of your face, lips, tongue or throat; or a severe skin reaction (fever, sore throat, burning eyes), get medical help immediately.

Both Cymbalta and Zoloft might cause vision changes including blurred vision or tunnel vision. If these occur along with eye pain/swelling/redness or seeing halos around lights it could be a sign of angle closure glaucoma which requires immediate medical attention.

If you experience any heart-related symptoms like fast/pounding/irregular heartbeat or shortness of breath while taking either drug make sure to seek out emergency medical aid.

Low sodium levels - indicated by headache/confusion/slurred speech/severe weakness/vomiting/loss of coordination/unsteady feeling - are more commonly associated with older adults taking SSRI and SNRI antidepressants but anyone experiencing these symptoms should seek prompt medical attention.

Lastly any signs of serotonin syndrome: agitation/hallucinations/fever/sweating/shivering/fast heart rate/muscle stiffness/twitching / loss of coordination/nausea/vomiting/diarrhea while on either medication warrants an immediate call for help as this is considered a serious condition which can be fatal if untreated.

What are the most common side effects for Cymbalta?

Cymbalta, another medication often prescribed for depression or anxiety disorders, can cause a range of side effects such as:

  • Dry mouth
  • Nausea and stomach upset
  • Constipation
  • Insomnia or sleep disturbances
  • Sweating more than usual
  • Feeling jittery or nervous
  • Increased heart rate
  • Changes in vision including blurriness
  • Ringing in your ears (tinnitus)
  • Irritability, agitation, restlessness
    Skin reactions like rash or itching. In some cases, Cymbalta may also lead to loss of appetite and consequential weight loss. It might increase urination frequency and cause headaches along with muscle pain. However, it is important to remember that each individual's reaction varies; hence not everyone will experience these symptoms.

Are there any potential serious side effects for Cymbalta?

Cymbalta, while generally well-tolerated, may cause potentially serious side effects in some people. If you experience any of the following symptoms whilst taking Cymbalta, seek immediate medical attention:

  • Signs indicative of a severe allergic reaction such as hives; difficulty breathing; swelling of your face, lips, tongue or throat
  • Unusual bleeding or bruising under the skin
  • Increased suicidal thoughts or self-harming behavior
  • A sudden and severe headache or confusion along with problems with vision, speech or balance (possible signs of a stroke)
  • Liver problems--nausea, upper stomach pain, itching, loss of appetite dark urine clay-colored stools jaundice (yellowing of the skin or eyes)
  • High levels of serotonin in the body--agitation hallucinations fever fast heart rate overactive reflexes nausea vomiting diarrhea loss of coordination fainting.

These are not common side effects but they can occur. Always communicate with your healthcare provider about anything unusual you might be experiencing after starting a new medication like Cymbalta.

Contraindications for Zoloft and Cymbalta?

Both Zoloft and Cymbalta, like other antidepressant medications, may intensify symptoms of depression in some individuals. If you observe a worsening of your depression or an increase in suicidal thoughts or behaviors, please seek immediate medical consultation.

Zoloft and Cymbalta should not be consumed if you are taking or have recently taken monoamine oxidase (MAO) inhibitors. It is critical to inform your doctor about all the medications you are currently on; MAOIs will need approximately five weeks to flush out from your system to avoid potential harmful interactions with Zoloft and Cymbalta.

How much do Zoloft and Cymbalta cost?

For the brand name versions of these drugs:

  • The price of 30 tablets of Zoloft (50 mg) averages around $340, which works out to approximately $11–22/day, depending on your dose.
  • The price for a month's supply (28 capsules) of Cymbalta (60 mg) is about $475, working out to approximately $17/day.

Thus, if you are in the higher dosage range for Zoloft (i.e., 200 mg/day or higher), then branded Cymbalta may be less expensive on a per-day treatment basis. Please note that cost should not be a primary consideration in determining which drug is right for you.

For the generic versions - sertraline and duloxetine respectively - costs are significantly lower:

  • Sertraline is available in packs ranging from 30 to 90 tablets with approximate costs between $0.10 to $2.50 per day depending on whether you're taking an average dose between 50mg and 200mg daily.
  • Duloxetine comes usually in packs of either 30 or 60 capsules with prices starting at as low as $.20/day up to roughly $3.00/day based on typical dosages that can range from anywhere between 20mg and up to even120 mg daily.

Popularity of Zoloft and Cymbalta

Sertraline, more commonly known by the brand name Zoloft, was estimated to have been prescribed to about 38.7 million people in the US in 2020. Sertraline accounted for just over 23% of antidepressant prescriptions in the US and is classified as an SSRI (Selective Serotonin Reuptake Inhibitor). The prevalence of sertraline has been generally increasing since its approval by FDA in 1991.

Duloxetine, including brand versions such as Cymbalta, was prescribed to approximately 15.4 million people in the USA in 2020. As a SNRI (Serotonin-Norepinephrine Reuptake Inhibitor), duloxetine accounts for nearly half of all SNRI prescriptions and around under 10% of overall antidepressant prescriptions. The use of duloxetine has also seen a steady increase since its release due to its wider range of approved uses which include anxiety disorders, fibromyalgia and neuropathic pain along with major depressive disorder.


Both Zoloft (sertraline) and Cymbalta (duloxetine) have a long-standing record of usage in patients with depression, and are supported by numerous clinical studies indicating that they are more effective than placebo treatments. In some cases, the two drugs may be used together, but this is subject to careful consideration by a physician due to potential interactions. Because of their different mechanisms of action—Zoloft primarily affects serotonin while Cymbalta impacts both serotonin and norepinephrine—they tend to be prescribed under different circumstances. Zoloft is often considered a first-line treatment option for major depressive disorder and anxiety disorders, whereas Cymbalta would typically be considered as an additional therapy or in patients who did not respond well to SSRIs like Zoloft.

Both medications are available in generic form which represents significant cost savings especially for those paying out of pocket. Both Zoloft and Cymbalta require an adjustment period before effects become noticeable.

The side effect profiles between the two drugs bear similarities; however, each carries its own set of risks—with sexual dysfunction being more common with SSRIs such as Zoloft, whereas Cymbalta can lead to high blood pressure among others. For both drugs, it's important that patients closely monitor their moods when commencing treatment and seek immediate medical help if depression worsens or suicidal thoughts arise.