Vyvanse (Lisdexamfetamine) is a drug developed by Shire Pharmaceuticals as a successor to Adderall. Vyvanse was first approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in 2007. In 2015, Vyvanse was approved for binge eating disorder and was found to successfully minimize appetite and number of binge eating episodes per week compared to a placebo.
The drug has been investigated for a variety of other conditions, including the treatment of major depressive disorder. In fact, Shire Pharmaceuticals was fairly confident that the drug would be a success in treating depression, so much so that they conducted multiple late-stage clinical trials to determine its effectiveness as an adjunct. Unfortunately the trials were discontinued as a result of the drug’s poor efficacy.
The trials indicated that using Vyvanse with an antidepressant was no more effective than using a standalone SSRI or SNRI. Despite these findings, there is significant evidence that using psychostimulants as antidepressant augmentation strategies in cases of refractory depression is highly effective. Among individuals with depression that’s resistant to normative treatments, Vyvanse may provide some benefit.
Vyvanse for Depression: Lisdexamfetamine as an Adjunct
Many cases of refractory depression respond well when a psychostimulant is added as an adjunct. While a psychostimulant may not be even a first-line adjunct option, in many cases it is effective. Adding a psychostimulant to an existing antidepressant may improve energy, motivation, cognition, and address low dopamine levels that may be contributing to depression.
A majority of psychiatrists end up testing drugs like antipsychotics, mood stabilizers, and even thyroid hormone as an adjunct strategy for depression. However, these substances may exacerbate SSRI-induced side effects (e.g. weight gain, sluggishness, sexual dysfunction), a psychostimulant like Vyvanse may be a better adjunct. Furthermore, Vyvanse may counteract unwanted antidepressant-induced side effects (e.g. weight loss, sexual dysfunction, drowsiness).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22263621
Research Timeline: Vyvanse for Depression
The drug Vyvanse was slated to become an FDA approved adjunct treatment for depression, but was found ineffective in late stage clinical trials. That said, there have been numerous studies suggesting that Vyvanse may help with certain aspects of depression. It may be particularly beneficial for those with major depression and: comorbid ADHD, executive dysfunction, or lingering depressive symptoms during antidepressant treatment.
2011: A study published in 2011 investigated the safety and efficacy of Vyvanse (lisdexamfetamine) among individuals with ADHD that had a history of depression and/or substance use. Researchers gathered data of comorbid depression from medical history reports filed by clinicians. The study incorporated a randomized, double-blind, placebo-controlled design with forced titrations of Vyvanse.
Results from the study were analyzed based on ratings from the ADHD Rating Scale and Clinical Global Impressions Scale. Data was collected prior to treatment with Vyvanse, and following the treatment of 30 mg, 50 mg, or 70 mg. Outcomes indicated that Vyvanse produced the same effect among individuals regardless of whether they had a history of depression, substance abuse, or no comorbid condition.
Based on the results of this study, Vyvanse was able to eradicate attentional deficits just as significantly among individuals with a history of depression as those without one. While this is a small scale study, it highlights the fact that the drug may be particularly beneficial for those who have ADHD with comorbid depression or vice-versa. It remained unclear as to whether those with a history of depression were depressed at the time of the study, as well as whether mood improved as a result of Vyvanse treatment.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071091/
2013: Results from a randomized clinical trial were published that evaluated Vyvanse as an adjunct treatment for adults with residual depressive symptoms following treatment with Lexapro. The goal of this trial was to evaluate the safety and efficacy of Vyvanse in reducing lingering depressive symptoms that weren’t alleviated by Lexapro. A total of 129 adults participated in the study, and the Montgomery-Asberg Depression Rating Scale was administered to assess pre-trial, intra-trial, and post-trial depressive symptoms.
Results of the study suggested that the depressive symptoms of the 65 individuals receiving Vyvanse improved significantly when compared to the 64 individuals receiving a placebo. Researchers noted significant reductions in Montgomery-Asberg Depression Ratings after 14 weeks. Authors suggest that among individuals with inadequate responses to an antidepressant, adjunct treatment with Vyvanse may be an effective option.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24021497
2013: Another study was published in 2013 that specifically analyzed the effects of Vyvanse on body weight and metabolism. Their secondary objective was to analyze the effect of Vyvanse in reducing ADHD and depressive symptoms among individuals diagnosed with bipolar disorder (both type 1 and 2). The study consisted of 45 adults with bipolar disorder and comorbid ADHD with stable moods.
The study involved flexible dosing and was regarded as being open-label. All participants began with 30 mg of Vyvanse as an adjunct for the first week. Flexible dosing meant that some participants may have their dosage titrated upwards between 30 mg and 70 mg between Week 2 and Week 4 of the study.
The average dose of Vyvanse administered was 60 mg, and researchers noted a significant decrease in weight after 4 weeks when compared to baseline measures. The following measures also decreased when compared to baseline: body mass index, fasting total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol. Reductions in ADHD and depressive symptoms were considered significant after 4-weeks when compared to baseline measures.
This suggests that short-term (one month) treatment with Vyvanse may elicit favorable effects on body weight (e.g. weight loss) and body mass index. More importantly, the drug was considered effective in reducing both attentional deficits and depressive symptoms among those with bipolar disorder. This provides further evidence elucidating some benefit associated with using Vyvanse for depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24014142
2014: A study published in 2014 evaluated Vyvanse as an augmentation to antidepressant monotherapy among individuals with executive dysfunction with comorbid partial or fully remitted major depression. This was a randomized, placebo-controlled study with 143 adult participants. All individuals had been taking an antidepressant for at least 8 weeks and were assessed with the following measures: Montgomery-Asberg Depression Rating Scale (MADRS), Behavior Rating Inventory of Executive Function (BRIEF), and Self-Report-Global Executive Composite (GEC).
Following a preliminary screening period of 2 weeks, all participants were assigned to 9 weeks of either Vyvanse or a placebo as an adjunct, followed by a single-blind setup with just a placebo. A total of 119 individuals were able to complete the study, and statistically significant improvements were noted among the 60 individuals receiving Vyvanse compared to the 59 receiving a placebo. These improvements were significant among all rating scales: MADRS, BRIEF, and GEC.
Results suggest that among adults with executive dysfunction, and partial or fully remitted depression, Vyvanse significantly improved the executive dysfunction and further reduced depressive symptoms. Authors noted that Vyvanse had a relatively safe side effect profile and that the results were consistent with other findings. This means that if your depression is compromising your executive performance, Vyvanse may provide significant benefit.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24309905
2015: Newer research published in 2015 attempted to determine both the efficacy and tolerability of Vyvanse among individuals experiencing bipolar depression. In this study, 25 individuals with either Type 1 or Type 2 bipolar disorder enrolled in a randomized, placebo-controlled, double-blind study over the course of 8 weeks. Of these individuals, 11 were administered Vyvanse, while 14 were administered a placebo.
To determine the degree to which a person’s depression had improved, researchers assessed depressive symptoms using the Montgomery-Asberg Depression Scale. Results from the study suggested that there were no significant differences in terms of mood between the Vyvanse group and the placebo group based on Montgomery-Asberg Depression Scale ratings. That said, self-reports among those receiving the Vyvanse were notably different than those receiving the placebo.
Those administered the Vyvanse self-reported less depressive symptoms, reduced fatigue, less daytime sleepiness, and reductions in binge eating. Further data revealed that those taking the Vyvanse had reduced fasting levels of low-density lipoprotein and total cholesterol. Authors of the study indicate that Vyvanse was well-tolerated, but may have potential for abuse.
The subjective self-reports of reduced depression as a result of the Vyvanse should be worth noting. Additionally the small sample size of the study makes it difficult to determine the degree by which those receiving the Vyvanse differed from those receiving the placebo. There is a need for larger-scale, longer-term studies analyzing the effects of Vyvanse in treating bipolar depression.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25340384
How Vyvanse May Help Depression: Mechanisms of Action
Vyvanse may help alleviate certain depressive symptoms via its mechanism of action as a dopamine reuptake inhibitor and its ability to stimulate the release of presynaptic neurotransmitters. This provides an individual with increases in dopamine, that when combined with an SNRI are targeting the trifecta of serotonin, dopamine, and norepinephrine. In other words, you’re getting an effect akin to taking a “triple reuptake inhibitor” (SNDRI).
- CNS stimulation: Vyvanse is a potent CNS stimulant. The lisdexamfetamine is metabolized into dextroamphetamine and the amino acid l-lysine. The dextroamphetamine is what stimulates the central nervous system and increases your energy levels. This means that you’ll feel more activated, less tired, and your brain will be operating at a higher level than without the drug.
- Dopamine increase: For some individuals, a notable benefit resulting from the usage of psychostimulants like Vyvanse is a dopamine increase. Vyvanse substantially increases dopamine levels and activates dopamine receptors in the prefrontal cortex (D1 receptor). Some individuals may benefit significantly from the dopamine increase. In fact, certain people may find that dopamine not serotonin was the initial cause of their depression; targeting it with Vyvanse may help.
- Other neurotransmitter increases: Vyvanse is known to increase a variety of other neurotransmitter concentrations, most notably norepinephrine. There is speculation that low norepinephrine and depression are linked. It also affects serotonin to a minor extent, eliciting subtle increases.
- Prefrontal activation: Those with depression and/or executive dysfunction often have impaired activation of the prefrontal cortex. The prefrontal cortex is the most advanced part of your brain that helps you with critical analysis, planning, thought organization, attention, and even mood. Vyvanse helps activate the prefrontal cortex, offsetting the effects that stem from hypoactivation – one of which may be depression.
- Triple reuptake inhibition: There’s a lot of buzz about new “SNDRI” drugs, but these shouldn’t be regarded as anything special. If you want to experience these triple reuptake inhibitors, you could theoretically just add Vyvanse to an SNRI. This will provide reuptake of serotonin, norepinephrine, and dopamine. Some people may find this advantageous over targeting just one neurotransmitter like serotonin.
Potential Benefits of Vyvanse as an adjunct
Below are some potential benefits associated with taking Vyvanse for depression. Many of these benefits may indirectly contribute to mood improvement as a result of improvements in realms such as: cognitive function, productivity, motivation, and weight loss.
- Cognitive enhancement: Vyvanse is well documented as a cognitive enhancer. In fact, taking it has been shown to increase IQ by an average of 4.5 IQ points among those with ADHD. While this improvement may not be permanent, it can provide a temporary boost to someone who is severely depressed that cannot think clearly. For some individuals, just enhancing cognition results in improved self-esteem and less depression.
- Counteracting side effects: Another obvious benefit associated with using Vyvanse is that it may counteract antidepressant-induced side effects. This means that if your antidepressant is causing weight gain, it may neutralize it or tip the scale towards weight loss. It also can improve antidepressant-induced brain fog, excessive drowsiness, or sexual dysfunction.
- Motivation boost: There’s also potential for Vyvanse to significantly increase your motivation. The dopamine increase as a result of this medication is believed to motivate us to achieve goals and avoid unfavorable outcomes. This means that you may feel more motivated to accomplish goals. Goal-oriented behavior is known to help offset depression and increase feelings of well-being.
- Productivity: Those taking Vyvanse may find that they are significantly more productive while taking it than they had in the past. This is due to the increase in prefrontal activation coupled with the dopaminergic and noradrenergic effects of the drug. When you feel more motivated, can think clearer, and your brain is performing at a higher level, your productivity will increase. Increasing productivity may lead to a better mood via feelings of accomplishment, achievement, or a pay increase at work.
- Sexual enhancement: Regardless of whether you find your antidepressant causing sexual dysfunction, Vyvanse has potential to help. It may enhance sexual function as a result of increasing dopamine and norepinephrine levels. This may result in a higher libido, improved sexual performance, or greater pleasure associated with sex.
- Socialization: Sometimes users may attain a pro-social effect from a drug like Vyvanse. This makes them feel increasingly confident in social situations as a result of heightened mental acuity. In other words, a person may feel more “primed” for conversation and derive more pleasure from social interactions than they had in the past.
- Weight loss: There is significant evidence linking Vyvanse and weight loss. The drug is known to curb binge eating episodes, reduce appetite, speed metabolism, and provide you with increased energy for working out. Although it shouldn’t be used solely for weight loss, the added benefit of weight loss could theoretically translate to an improved mood.
Optimal scenarios to use Vyvanse for depression
There are several types of depression that may respond better to Vyvanse as an adjunct than others. Since Vyvanse is approved to treat ADHD and binge eating disorder, individuals with those conditions may experience an indirect mood boost from getting their attentional deficit or binge eating under control.
- ADHD: If you have ADHD, medicating your attention-deficit and/or hyperactivity may benefit your depression. Some individuals with ADHD may find that when their attention span increases, they feel less depressed. ADHD can cause depression, or occur entirely separate from depression. In any regard, those with ADHD and comorbid depression or depression with comorbid ADHD may stand to benefit from Vyvanse.
- Binge eating disorder: In 2015 Vyvanse was approved by the FDA for the treatment of binge eating disorder (BED). Those who experience depression related to their binge eating may feel less depressed when Vyvanse gets their binge eating under control. That said, even if the binge eating and depression are mutually exclusive conditions, it’s possible that the Vyvanse may alleviate certain aspects of depression.
- Dopaminergic depression: If you have abnormally low levels of dopamine, working to increase dopamine may offset many of your depressive symptoms. Although natural methods for increasing dopamine may provide benefit, they are not as potent as Vyvanse. For individuals that are believed to have an atypical dopaminergic depression, Vyvanse may be a preferred treatment.
- Fatigue-based symptoms: Just because Vyvanse isn’t approved to treat narcolepsy or excessive daytime sleepiness doesn’t render it ineffective for those conditions. The active ingredient resulting from the breakdown of Vyvanse is dextroamphetamine, which has been used to reduce sleepiness and fatigue since World War II. If you have a fatigue-based depression, Vyvanse may help combat your tiredness.
- Treatment-resistant depression: Those with depression that is resistant to traditional treatments may respond well when adding Vyvanse to antidepressant monotherapy. Sometimes there’s a symbiotic or synergistic reaction between various medications and their ability to reduce depression. Adding Vyvanse to an existing antidepressant may provide significant benefit to those with refractory depression.
Why you may want to avoid Vyvanse for depression
Not every person with depression will respond well to Vyvanse. In some cases, Vyvanse may exacerbate depressive symptoms or even worsen comorbid conditions like anxiety. For others, the drug may lead to abuse, addiction, and/or dependence – potentially increasing depression.
- Abuse potential: Vyvanse is classified as a “Schedule II” controlled-substance. This means that it has a high potential for abuse. The potential for abuse stems from the dopaminergic rush that the drug provides, creating a temporary euphoria for abusers. Abuse may result in abnormally high dopamine levels and ultimately may trigger stimulant psychosis.
- Addiction: If you have an addictive personality, this may be the wrong drug to try. Many people become addicted to its stimulatory effects and they continue to seek out Vyvanse or other stimulants. If you are constantly thinking about taking your next Vyvanse pill or getting your next dextroamphetamine fix, this probably isn’t a good fit.
- Anxiety: Many individuals with depression have comorbid anxiety. In rare cases, a person’s anxiety may actually improve from Vyvanse, but this is uncommon. In most cases, an individual will feel a heightened sense of anxiety, nervousness, and discomfort.
- Dependence: Over time, it is highly possible to become dependent upon Vyvanse for functioning. This means that you may come to rely on the drug in order to perform (at school or work), socialize, or even stay alert throughout the day. This dependence is most often psychological in that a person feels they need the drug to mentally function, but may also be physical.
- Insomnia: Another potential drawback associated with Vyvanse is that it may throw off your sleep cycle as a result of insomnia. Sure the stimulation from the drug may improve your depression, but it may also lead to an inability to sleep or broken sleep. Difficulties with sleep can exacerbate depression and lead to other health problems.
- Long-term effects: The long-term effects associated with psychostimulant usage may be undesirable, particularly for those without ADHD. Over time, your brain may downregulate dopamine receptors and burn up endogenous dopamine stores as a result of the Vyvanse. This means that over the long-term, you may be digging yourself in a dopaminergic hole that will be difficult to escape.
- Refill difficulty: Due to the fact that Vyvanse is a “Schedule II” drug, refills are not available. This means that you must have a physical signed copy of a prescription from your psychiatrist for each 30 day supply of Vyvanse. If you aren’t able to see your psychiatrist within a month, you may experience temporary withdrawals.
- Side effects: Some people don’t react well when taking psychostimulants. Vyvanse may make them feel jittery, jumpy, or restless. In other cases, a person may experience headaches, dizziness, or excess sweating. If the side effects become unbearable, this drug may not be a good option.
- Tolerance: It is relatively easy to build up tolerance to the effects of dextroamphetamine. This means that you may need to frequently increase your Vyvanse dosing to alleviate your depressive symptoms. Once tolerance is established to the highest dose, you may find that you get no additional relief from the drug.
- Withdrawal: The discontinuation associated with stopping Vyvanse shouldn’t be minimized. Those that have taken the drug for a long-term, especially at a high dose are likely to experience debilitating Vyvanse withdrawal symptoms. These include increases in fatigue, sleepiness, and cognitive impairment. In many cases the withdrawals will be more severe than the symptoms experienced prior to taking the drug.
How does Vyvanse compare to Adderall for depression?
In the past, many psychiatrists utilized Adderall for depression as a psychostimulant adjunct. Adderall is very similar to Vyvanse in that it contains dextroamphetamine (75%), but also contains levoamphetamine (25%). Vyvanse is a prodrug, meaning it is biologically inactive until orally ingested. Upon ingestion, the drug takes nearly 2 hours before it is metabolized into dextroamphetamine and l-lysine.
Vyvanse is considered to have a slightly lower potential for abuse, is slightly less potent, and a longer duration of effect by comparison. For more information, you can check out the comparison article I wrote called “Adderall vs. Vyvanse.” Neither Vyvanse nor Adderall should be regarded as superior to the other for depression – responses are largely subject to individual variation.
How does Vyvanse compare to Provigil for depression?
Vyvanse differs from Provigil in that it has a greater potential for abuse and dependence. Provigil doesn’t provide as significant of a dopamine kick and has a shorter duration of effect by comparison. That said, Provigil may be the preferred choice by some psychiatrists due to the fact that it doesn’t have as significant abuse potential, has less intense side effects, and minimal withdrawal symptoms (by comparison).
Some individuals may respond better to the mechanisms of Provigil better than Vyvanse or vice-versa. For additional information, read “Provigil for depression.”
Personal Experience Taking Vyvanse for Depression
For several months, I took Vyvanse on an intermittent basis to treat depression. Although it was meant to be used as an adjunct, I used it intermittently as a standalone option. I wasn’t too keen on continuing with my antidepressant due to undesirable side effects, so I stopped it and only used Vyvanse as needed.
Due to the potential for abuse, I used an extremely low dose by taking a 30 mg capsule and pouring the powder into yogurt – this was recommended by my psychiatrist. I probably was taking somewhere around 10 mg to 15 mg and experienced noticeable benefit. It may not have made me feel “happy” or “euphoric” like Adderall did, but it certainly alleviated my depression.
It dramatically increased my mental clarity, optimism, and cognitive function. Despite my experience with low dose Vyvanse for depression, I never wanted to become dependent upon it or fall victim to the long-term trap of downregulation of dopamine receptors and low dopamine levels. That said, nearly every time I took it, it eradicated my suicidal thoughts and depression, while simultaneously giving me hope for the future.
Verdict: Vyvanse may be an effective adjunct treatment for depression
Despite the fact that formal FDA approval wasn’t granted to Vyvanse as an adjunct treatment for major depression, there is evidence suggesting that it may be helpful for select individuals – particularly those with treatment-resistant depression. Additionally, those that have comorbidities of ADHD, binge eating disorder, executive dysfunction, or fatigue may derive significant benefit from Vyvanse. Certainly this drug shouldn’t be used in everyone, particularly those with addictive personalities.
That said, if a psychostimulant is to be used as an adjunct, Vyvanse may be a preferred option over older drugs. This is due to the fact that it is a prodrug, is believed to have a smoother absorption, is less likely to make a person “crash,” and has a long duration of effect. However, some psychiatrists may still prefer Provigil (modafinil) over Schedule II substances like Vyvanse due to its well established efficacy and reduced abuse potential.
Have you found Vyvanse helpful for depression?
If you have personally used Vyvanse (Lisdexamfetamine) to help treat your depression, feel free to share your experience in the comments section below. For those that are taking Vyvanse as an adjunct, what benefits were most pronounced when you started taking it? Did you find the drug effective at offsetting SSRI or SNRI-based side effects? Keep in mind that some people may find that Vyvanse worsens their depression, if you disliked this drug’s effect on your mood, be sure to explain.