In our last blog post, we explored the general topic of treatment resistant depression (TRD), which affects millions of people around the world. For this article, let’s take a deep dive into one of the treatment options I consider in my practice as a depression doctor – pramipexole.

While feeling sad from time to time is an unavoidable part of life, people with depression, such as a major depressive disorder, experience persistent and overwhelming symptoms that interfere with daily functioning, relationships and overall quality of life.

If persistent feelings of sadness, depression or feelings of emptiness are reducing your enjoyment of life, there are many treatment options, including medications. However, for those with TRD, this is a form of major depressive disorder (MDD) that doesn't improve after trying at least two different antidepressant treatments, taken at adequate doses and duration.
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In other words, even after following standard plans for treating depression, including medications and often talk therapy, people with TRD continue to experience significant symptoms of depression. TRD may require alternative approaches, one of which could be pramipexole.

This is a prescription medication that acts as a dopamine agonist, or rather, it mimics what dopamine does in our brains. Dopamine is a chemical messenger in the brain known as a neurotransmitter. It helps nerve cells send signals to each other and plays a key role in how we feel, move, and think.
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Here are a few important things dopamine does:

• Movement: It helps control smooth, coordinated body movements. Low dopamine levels are linked to Parkinson’s disease.
• Mood and Motivation: Dopamine is part of the brain’s “reward system,” which makes us feel pleasure and motivation. It plays a role in how we experience happiness and satisfaction.
• Learning and Attention: It helps with focus, memory, and learning new things.

Too little dopamine can cause problems like depression or trouble moving. Too much dopamine may be linked to conditions like schizophrenia or addiction. Pramipexole was designed to help people with too little dopamine, specifically for those with Parkinson’s disease and Restless Leg Syndrome (RLS).

While pramipexole (brand names include Mirapex, Pexola and Sifrol) is FDA-approved for Parkinson’s and RLS, this drug has shown potential to help some people with treatment-resistant depression (TRD), especially when used as an add-on (augmentation) to standard antidepressants.

Here's how it may help:

• Dopamine support: Pramipexole boosts dopamine activity, which can improve mood and motivation, areas that often affect people with TRD.
• Clinical studies: Some small studies and case reports have found that adding pramipexole helped reduce symptoms of depression in people who didn’t respond to traditional treatments.

​Pramipexole tends to be best suited for people whose depression includes symptoms such as low energy, lack of motivation (anhedonia), or who haven't responded well to SSRIs or SNRIs.

Pramipexole is not FDA-approved specifically for depression, so it’s used off-label for TRD. The FDA approves medications for specific uses based on research. But once a drug is approved, doctors are legally allowed to use their medical judgment to prescribe it for other reasons if they believe it could help. Off-label use is common in psychiatry, especially when standard treatments haven’t worked.
Pramipexole is an excellent example. This drug is FDA-approved for Parkinson’s disease and RLS. But some doctors may use it off-label to treat treatment-resistant depression, because studies and experience suggest it might help, even though it wasn’t officially approved for that purpose.
If you're considering it for TRD, it should be discussed with a depression psychiatrist who has experience with off-label treatments. As an experienced depression doctor, I have found that pramipexole can be an excellent option for some patients with TRD.
Keep in mind that this drug, as with all medications, may come with potential risks and side effects. Here’s a quick look at some of the most common side effects as well as more serious concerns.

Common Side Effects of Pramipexole

• Drowsiness or sudden sleep attacks – Some people fall asleep without warning, even during the day.
• Dizziness or lightheadedness, especially when standing up (orthostatic hypotension).
• Nausea or upset stomach (this typically resolves within a few weeks of taking the drug)
• Fatigue or weakness
• Constipation
• Hallucinations – Seeing or hearing things that aren’t there, especially in older adults. (This side effect is more common in Parkinson’s patients or patients with a history of psychosis or bipolar disorder.)

Serious Risks

• Impulse control disorders – Some people may develop strong urges they can’t control, like gambling, excessive shopping, binge eating, or hypersexuality.
• Sleep problems – Including insomnia or abnormal dreams.
• Low blood pressure – Can cause fainting or falls.
• Confusion or changes in mood or behavior, especially in older adults or those with psychiatric conditions.

Special Caution
People with kidney problems may need lower doses since the drug is cleared from the body by the kidneys.
Because of these risks, pramipexole should always be taken under close medical supervision, especially when used off-label for conditions like treatment-resistant depression.

​Pramipexole can interact with several medications, which may increase side effects or reduce the effectiveness of one or both drugs. Here are some important categories and examples to be aware of:

Drugs that affect the brain or nervous system:
These can increase drowsiness, confusion, or the risk of hallucinations:
Sedatives (e.g., benzodiazepines like lorazepam or sleep aids like zolpidem)
Antidepressants (especially oral antidepressants such as tricyclics and MAOIs)
Antipsychotics (e.g., haloperidol, risperidone) may reduce pramipexole’s effects
Other dopamine agonists (risk of additive side effects)
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Drugs that lower blood pressure:
These can worsen dizziness or fainting from pramipexole:

• Blood pressure medications (e.g., lisinopril, amlodipine)
• Diuretics (e.g., furosemide)

Drugs that affect kidney function:
​Again, because pramipexole is cleared by the kidneys, drugs that impair kidney function can raise pramipexole levels:

• NSAIDs (e.g., ibuprofen, naproxen) in high or long-term doses
• Certain antibiotics (like aminoglycosides)

Other potential interactions:

• Alcohol: Can worsen drowsiness and dizziness.
• Cimetidine (used for heartburn): May slow pramipexole’s clearance, increasing its effects. This over-the-counter drug also is known by its brand name Tagamet.

Now that you’ve read about the risks, which can seem scary, let me assure you that not every patient experiences all or even any of those side effects. However, when I prescribe any medication for patients, it is crucial that they disclose all of the medications and supplements they are taking.  Additionally, if you use any recreational drugs – alcohol, marijuana, etc., it is important to disclose this as well.

Remember, I am here to help you, not to judge. Many people, especially those with mental health issues, turn to drugs or alcohol to alleviate symptoms. Unfortunately, alcohol and recreational drugs often can make mental illness worse and they often are dangerous to use in conjunction with prescribed medications and even some over-the-counter medicines.
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As a depression psychiatrist, it’s crucial that I have all of the information so that I can create a truly effective treatment plan. Keep in mind, if you are struggling with drug use or alcohol use, I do work as an addiction psychiatrist, as well, and treating all of the issues you are facing is the best way to improve your life. It’s certainly not easy, but tackling these challenging issues can improve your level of happiness as well as your relationships with family and friends.

Typically, this drug is not given on its own but in combination with a standard antidepressant. Generally, it is prescribed along with one of the following classes of antidepressants.  These medications work on serotonin and/or norepinephrine, while pramipexole targets dopamine, providing a broader neurochemical effect.

Selective Serotonin Reuptake Inhibitors (SSRIs)
Sertraline (Zoloft)
Fluoxetine (Prozac)
Escitalopram (Lexapro)
Citalopram (Celexa)
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Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Venlafaxine (Effexor XR)
Duloxetine (Cymbalta)

Atypical Antidepressants
Bupropion (Wellbutrin) – especially common, since it also works on dopamine and norepinephrine
​Mirtazapine (Remeron) – sometimes combined to address sleep and appetite issues

If you are struggling with TRD, the first step is to reach out to a depression doctor for a thorough diagnosis. A psychiatrist can examine all aspects of your health, including physical and mental health issues, as well as review previous treatment plans.
Keep in mind, if I determine that pramipexole is not the right option for you, there are many other options these days for people with TRD. For instance, we might try intranasal ketamine, transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT) or perhaps even psilocybin.
Generally, as a psychiatrist for depression, I also recommend adding talk therapy and lifestyle changes to your treatment plan. Exercise, exposure to sunlight, meditation, proper nutrition and other steps can help people better manage the symptoms of major depression.

While it can take time to find the ideal approach for your TRD, there is hope, and many patients find that pramipexole or another treatment option greatly reduces symptoms and allows them to live a happier, healthier life.
If you are searching for a depression doctor, I can help. I work as a psychiatrist in Thousand Oaks, as well as a psychiatrist in Westlake Village, Simi Valley and throughout north LA county and southern Ventura county. I have extensive experience treating depression, including TRD, as well as anxiety, bipolar disorders, eating disorders, addiction and the complexity of treating co-occurring disorders.

Humans are inherently social creatures, but if you’ve been feeling disconnected and lonely, this can impact your quality of life significantly. As a depression doctor, I believe it’s important for all of us to understand the impact of loneliness, but also to find ways to combat these feelings of isolation.

Loneliness can be a significant factor in the development of depression. While loneliness itself is a state of feeling disconnected, isolated, or separated from others, it can lead to various mental health issues, including depression. As a psychiatrist for depression, I’ve seen firsthand how loneliness impacts our lives. Here are just a few ways that feelings of loneliness can affect our psyche and lead to depression. ​

• Holiday & Seasonal Depression: For many people, the holidays and the winter season can be a difficult and problematic time, and this is especially true for those suffering from depression. The holidays are meant to be happy occasions, but they often make us feel sad, stressed out and alone.
  
  Additionally,  the lack of daylight during the winter months, and weather that often necessitates staying indoors, also can impact our well-being, leading to feelings of sadness and even full-blown depression. If depression haunts you seasonally, this is known as Seasonal Affective Disorder, and it’s very common. 
• Genetic Predisposition: A family history of depression can increase the risk, suggesting a genetic component to the disorder. 
• Brain Chemistry and Neurotransmitters: Imbalances in the brain's neurotransmitters, such as serotonin, norepinephrine, and dopamine, are believed to play a crucial role in depression. 
• Hormonal Changes: Changes in hormone levels, due to thyroid problems, menopause, childbirth (postpartum depression), or other health conditions, can trigger depression. 
• Life Events: Traumatic or stressful life events, including the loss of a loved one, financial problems, divorce, or significant life changes, can precipitate depression. 
• Chronic Illnesses: Living with chronic pain or a chronic illness, such as diabetes, heart disease, or cancer, can lead to feelings of hopelessness and depression. 
• Substance Abuse: Alcohol or drug abuse can both be a cause and a result of depression. Substance use can exacerbate or trigger depressive episodes. 
• Personality Traits: Individuals with certain personality traits, such as low self-esteem, being overly dependent, self-critical, or pessimistic, are at a higher risk of developing depression. 
• Trauma and Abuse: Experiencing trauma, abuse (whether physical, emotional, or sexual), or neglect, especially in early life, can significantly increase the likelihood of developing depression later in life.
• Social Factors: Poor social support, isolation, and conflict in relationships can contribute to the development of depression.

As a psychiatrist for depression, I work diligently to identify the root causes of a patient’s depression. In some cases, several of these factors can contribute to the development of depression. However, when we can identify the causes, this generally makes treatment more effective. 

If feelings of loneliness and isolation are at the root of your depression, there are some proactive steps you can take to connect with others, engage in meaningful activities and address underlying feelings of isolation. Here are several strategies to help alleviate loneliness:

1. Reach Out to Family and Friends: Make an effort to connect or reconnect with family and friends. Regular phone calls, messages, or video chats can help reduce feelings of isolation. Sometimes family members and friends are unaware of your level of loneliness, which is why you often have to be the person taking that first step. Once you connect, ask if you can schedule a regular phone call or video call or perhaps a weekly lunch or dinner.
2. Join Groups or Clubs: Participate in groups or clubs that align with your interests or hobbies. This can be a great way to meet new people who share similar passions.
3. Volunteer: Volunteering for causes you care about can connect you with others and provide a sense of purpose and community. 
4. Stay Active: Physical activity can boost mood and reduce feelings of loneliness. Joining exercise classes, yoga classes, dance classes or sports clubs can also introduce you to new friends. 
5. Explore New Interests: Taking classes or learning new skills can help you meet people, increase your self-confidence, and reduce feelings of loneliness. 
6. Attend Social Events: Make an effort to attend social gatherings, even if it feels daunting. Each event is an opportunity to connect with others. 
7. Consider a Pet: Pets can offer companionship, unconditional love, and a sense of responsibility. They also can be a way to meet other pet owners. 
8. Online Communities and Support Groups: Joining online forums or support groups related to your interests or experiences can offer a sense of belonging and connection. 
9. Practice Self-Compassion: Be kind to yourself and recognize that feeling lonely is a common human experience. Engage in self-care practices that nurture your well-being. 
10. Make Use of Technology: Use technology wisely to connect with others, but be mindful of screen time. Social media can be a tool for connection, but it's important to seek meaningful interactions. 
11. Create a Routine: Establishing a routine can provide structure and purpose, reducing feelings of aimlessness that can accompany loneliness. 
12. Seek Professional Help: If loneliness is persistent and affecting your mental health, consider talking to a mental health professional. Therapy can provide strategies to cope with loneliness and address any underlying issues.

​Combating loneliness is a process, and what works for one person might not work for another. It's important to try various strategies and find what best suits your personality and lifestyle. Remember, seeking connection and community is a fundamental human need, and taking steps to address loneliness is a brave and worthwhile endeavor. It’s not easy to reach out, but it’s also not easy to suffer from loneliness and depression.

Seeking treatment for depression or loneliness is an important step toward improving your mental health and overall well-being. Here are some signs and situations when it's advisable to seek professional help from a local psychiatrist:

​Whether you are dealing with persistent loneliness and/or depression, scheduling an appointment with a psychiatrist for depression is always a good idea. You also can talk with your primary care provider or a therapist.
 
As a psychiatrist for depression, I can provide you with a thorough diagnosis as well as create a treatment plan that addresses all of the issues you are facing. A depression psychiatrist also can provide you with medications, if needed.
 
Many different medications and combinations of medication can treat depression successfully. Talk therapy, dialectical behavior therapy and cognitive behavioral therapy can be helpful, as well. Even with medication, meeting with a depression therapist or psychologist is encouraged as a combination approach tends to yield the best results.
 
If you find that medications and therapy aren’t alleviating your symptoms, there are other options to consider, such as ketamine therapy and eye movement desensitization and reprocessing (EMDR). Other options, such as repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS), also can be beneficial for those with treatment-resistant depression.
 
If you are struggling with deep feelings of loneliness and despair, it’s best to contact a psychiatrist for depression as quickly as possible. As a depression doctor, I have successfully treated many patients with depression and chronic loneliness, and there is always hope for a brighter future. I also work as a PTSD psychiatrist and anxiety psychiatrist, which often co-occur with depression. I also can treat bipolar disorder, eating disorders, borderline personality disorder or any other co-occurring disorder.
 
I offer both in-person services as a psychiatrist in Thousand Oaks, as well as telepsychiatry, which can be a very convenient option to consider. Don’t wait another day to seek help. Depression and these feelings of loneliness can be tackled, and while it can take time to find a treatment that works, you are worth it and all you have to do is take the first step and give our office a call.