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Beyond Antidepressants: Four Scientifically-Proven Alternatives to Antidepressants

Why do we need alternatives to antidepressants? Antidepressants, though widely used, have limitations in efficacy, side effects, slow onset, and withdrawal issues. This article explores exercise, and transcranial magnetic stimulation (TMS), psychedelic-assisted therapy, and ketamine therapy as proven alternatives. Discover their benefits and drawbacks, including faster results and fewer side effects. Consider these alternatives to personalize your approach to treating depression.

Why do we need antidepressant alternatives?

Antidepressant medications, like SSRIs and MAOIs, have long been the primary treatment option for people grappling with depression.

While these provide relief for many, they do not work equally well for everyone. 

These are four of the most common reasons why:

  • Limited efficacy and treatment resistance
  • Unwanted side effects
  • Slow onset of action
  • Withdrawal issues and depression relapse

Limited efficacy and treatment resistance

For a significant proportion of patients, antidepressant treatments alone do not lead to substantial improvement.

This is called treatment-resistant depression. It affects up to a third of depressed patients and can be incredibly disheartening.

Treatment resistance occurs due to various factors, such as genetic predispositions, the severity of the depression, or coexisting conditions.

Side effects and tolerability issues

Antidepressants can cause a range of side effects, such as nausea, weight gain or loss, sexual dysfunction, drowsiness, and emotional blunting, to name just a few.

The burden of these side effects can be immense. So, even if someone feels like antidepressants alleviate some of their original symptoms, they may now be faced with new challenges.

Slow onset of action

Traditional antidepressants often take weeks or even months before their full therapeutic effects are realized.

When someone is experiencing acute distress, this slow onset of action is frustrating. The delay in symptom relief can contribute to a sense of hopelessness, driving individuals to seek faster-acting alternatives.

Discontinuation and withdrawal challenges

Even when tapering off gradually, discontinuing antidepressant medication can sometimes lead to antidepressant discontinuation symptoms. Possible withdrawal symptoms include dizziness, headaches, and flu-like sensations, as well as changes in affect, such as low mood, irritability, and anxiety.

Perhaps even more concerning is that individuals who stop taking antidepressants are more likely to experience a depressive relapse – bringing back the original symptoms that led them to take antidepressants in the first place.

4 Scientifically-Proven Alternatives to Antidepressants


In recent years, exercise has gained recognition as a natural remedy for depression, leading more physicians to “prescribe” it as a medicine for depressive symptoms.

While exercise may not be enough for someone with severe depression, for others, it has proven to be just as effective as regular antidepressant medications.

There is often discussion about how high-intensity exercise triggers the release of endorphins, the so-called body’s feel-good chemicals.

However, low-intensity exercise can be just as impactful in its own way as it stimulates the release of brain-derived neurotrophic factors (BDNFs) – proteins that facilitate the growth of nerve cells and the formation of new connections in the brain. This paves the way for new patterns of thoughts and behaviors to be learned and consolidated.

Of course, there is a significant hurdle to overcome here: depression tends to go hand in hand with low motivation and energy.

Even when we feel good, it is at times challenging to get out of bed to exercise on a daily basis. Having to find this willpower when we are depressed can then seem insurmountable.

This is one of the many reasons why the cycle of depression is so hard to break.

Transcranial Magnetic Stimulation (TMS)

Transcranial Magnetic Stimulation is a non-invasive procedure that uses magnetic fields to stimulate specific areas of the brain, typically the prefrontal cortex.

This stimulation is believed to modulate brain activity and restore the balance of neurotransmitters associated with mood regulation. This can lead to a reduction in symptoms such as sadness, hopelessness, and loss of interest.

Unlike traditional antidepressant medications that affect the entire body, TMS specifically targets the brain regions implicated in depression. This localized treatment approach may result in fewer widespread side effects.

While TMS is generally considered safe, there are some downsides to consider.

For one, it may cause scalp discomfort or headache at the site of stimulation. These side effects are usually transient, but more serious ones, like seizures and sudden mood changes, have also been reported. These are considered to be very rare, however.

TMS treatment can also be time-consuming as it typically requires multiple sessions over several weeks, often on an almost daily basis.

Finally, TMS can be a relatively costly treatment, and insurance coverage may vary.

Psychedelic-Assisted Therapy

Psychedelic-assisted therapy involves the controlled use of psychedelic substances in therapeutic settings.

While the exact mechanisms underlying psychedelics’ therapeutic potential remain somewhat of a mystery, one main way through which this may happen is through modulating the activity in the Default Mode Network (DMN) – an interconnected group of brain regions that are thought to contribute to internal modes of cognition used when remembering, thinking about the future, and mind wandering. This temporary alteration is believed to loosen overly rigid, negative patterns of thoughts and behavior that are typically associated with depression.

Like exercise, psychedelics promote neuroplasticity – the brain’s ability to reorganize and strengthen neural connections and form new ones.

Psychedelics can also facilitate therapeutic breakthroughs by provoking spiritual and personal insights, allowing participants to access suppressed emotions and thoughts and gain new perspectives on themselves and their lives.

A controlled and supportive set and setting are essential to ensure one’s safety and well-being, and they are recognized as important factors in producing therapeutic benefits. But for some people with certain underlying vulnerabilities, this might not be enough.

For example, psychedelics may worsen existing symptoms for individuals with severe mental health conditions or those at risk of psychosis.

In others, the substances’ unpredictable nature may lead to adverse reactions, such as anxiety and paranoia.

Ketamine-Assisted Therapy

Ketamine-assisted therapy has gained attention as a potential treatment for depression, with one significant advantage being its rapid onset of action. In contrast to traditional antidepressants, ketamine elicits rapid improvements in mood, often within hours after administration. This is extremely beneficial in cases where immediate treatment is needed, such as cases of suicidal ideation.

Ketamine has also shown particular promise in providing symptom relief in treatment-resistant depression, providing hope for individuals who have not responded to conventional antidepressants. 

Like psychedelics, the exact way in which ketamine provokes its antidepressant effects is yet to be fully known. Nonetheless, the responsible mechanism is likely mediated by ketamine’s effects on glutamate via NMDA receptors in the brain. These receptors are assigned an important role in aspects of synaptic plasticity and memory formation.


In a world where traditional antidepressant medications don’t work equally well for everyone, scientifically-proven alternatives offer new paths to well-being. Some of their benefits include faster results, fewer side effects, and targeted treatment approaches.

As with most things in life, they also have their potential drawbacks, however. These should all be weighed up and carefully considered when thinking about one’s treatment options for depression.

The professionals at the Psychedelica Collective specialize in ketamine-assisted therapy in Los Angeles for a wide range of mental disorders including treatment-resistant depression, PTSD, anxiety, OCD, and many more. For more information or to find out if you are a good candidate for treatment, contact us today to schedule a free 15-min consultation with a clinician.