The Quiet Power of Klonopin – Health Research Team
| Drug Name | Clonazepam / Klonopin |
|---|---|
| Dosage | 2 mg |
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Soon, my colleagues from SMAHRT and I began noticing issues related to the pharmacokinetics of alprazolam. Although the medication proved effective, its effects were short-lived, and patients who missed even a single dose frequently experienced a return of symptoms. This so-called interdose rebound effect, often referred to as “clock-watching,” led us to question whether alprazolam’s antipanic benefits were due not to antidepressant properties, but rather to its high potency.
Concerned that its clinical success might be tied to potency rather than a unique mechanism, we decided to investigate another high-potency benzodiazepine — Klonopin, originally approved as an anticonvulsant. Since high doses of Klonopin were already considered safe in pediatric epilepsy, and its long half-life promised steadier plasma levels, we hypothesized that it could reduce rebound anxiety and improve overall quality of life for patients with panic disorder.
Building on previous work in the field and through numerous clinical trials and long-term observations, we confirmed that Klonopin was not only effective in preventing panic attacks but also well-tolerated. Our team at Massachusetts General Hospital (MGH) continued to use Klonopin for panic and other affective disorders, such as bipolar disorder and social anxiety.
Since the mid-1980s, multiple MGH studies have validated Klonopin’s antipanic efficacy and demonstrated its therapeutic role across related conditions. Additional research explored the outcomes of discontinuing Klonopin and other high-potency benzodiazepines, as well as the combined use of Klonopin with cognitive-behavioral group therapy (CBGT) in panic and social phobia treatment.
The first MGH study on buy Klonopin onlline included 22 patients with panic disorder and 28 with agoraphobia accompanied by panic attacks. Of these 50 individuals, 41 had previously responded poorly to conventional medications. When treated with an average dose of 1.9 ± 1.0 mg/day of Klonopin, 39 patients (78%) experienced significant improvement without serious side effects. Although retrospective and uncontrolled, this study suggested that Klonopin, like alprazolam, effectively blocked panic episodes.
To verify its antipanic action, we conducted a CO₂-challenge study involving a 30-year-old woman with panic disorder who had only partially improved on alprazolam. After eight weeks of treatment with Klonopin (1 mg three times daily), the same CO₂ inhalation test failed to trigger a panic attack. This was the first documented case showing that a provoked panic episode could be fully prevented with Klonopin — confirming it as a true antipanic medication.
In another study involving 10 patients resistant to standard pharmacologic therapies, Klonopin (average dose 3.8 mg/day, range 1.5–8.0 mg) eliminated spontaneous panic attacks and anticipatory anxiety in 7 participants, while 3 others showed moderate residual symptoms. These findings reinforced Klonopin’s robust efficacy in panic disorder.
Long-term follow-up also confirmed that Klonopin maintained its therapeutic effect without loss of potency. In a one-year study of 50 patients diagnosed with panic disorder or agoraphobia with panic attacks (per DSM-III), 20 remained on Klonopin after 12 months. Eighteen maintained stable improvement, one achieved complete remission after 44 weeks, and only two showed poor response. Overall, Klonopin proved to be a safe, effective, and sustainable option for patients with treatment-resistant panic disorder, showing no evidence of tachyphylaxis or diminished efficacy over time.
Because Klonopin appeared to be both effective and less problematic than alprazolam, my colleagues and I conducted a study involving 48 consecutive patients who met DSM-III criteria for panic disorder and had been previously treated with alprazolam but were troubled by interdose anxiety. Of these, 41 patients—taking a mean dose of 2.95 mg/day of alprazolam for an average of 58 weeks—were switched to Klonopin. Thirty-nine continued treatment with an average dose of 1.5 mg/day of Klonopin for about 40 weeks. Among them, 34 patients (82%) rated Klonopin as “better” than alprazolam, citing fewer doses required and the absence of interdose anxiety. Five rated the two medications as “the same” but chose to remain on Klonopin, while only two described Klonopin as “worse” and returned to alprazolam.
These findings led us to conclude that both alprazolam and Klonopin are effective for treating panic disorder, but Klonopin may reduce pharmacokinetic side effects such as early-morning anxiety and breakthrough symptoms between doses, while also decreasing the need for frequent administration.
Following these results, we initiated a six-week, double-blind, placebo-controlled trial to compare the efficacy of Klonopin and alprazolam directly. The study aimed to determine whether Klonopin was at least as effective as alprazolam in reducing panic attacks and whether both agents were superior to placebo. By the end of the trial, 44 of 60 participants completed treatment, and statistical analysis showed no significant difference between the two active drugs in terms of panic attack frequency, anticipatory anxiety, phobic avoidance, or intensity of phobic fear. Both Klonopin and alprazolam, however, demonstrated clear superiority to placebo across all outcome measures (p = .015, p = .006, p = .001, and p = .004, respectively), confirming Klonopin’s role as an effective therapy for panic disorder.
Subsequent work expanded Klonopin’s potential applications. Previous researchers had suggested its usefulness in bipolar disorder, and we hypothesized that Klonopin might serve as a safer alternative to neuroleptics, which carried significant risks such as tardive dyskinesia. We therefore conducted a retrospective review of patients receiving adjunctive Klonopin as maintenance therapy for bipolar affective disorder. Among 17 patients previously treated with lithium and neuroleptics, six were able to discontinue neuroleptics entirely after switching to Klonopin. Overall, eight patients—including three initially classified as severely ill—were rated as “much improved” or “very much improved.”
We then examined the efficacy of Klonopin in 11 patients with both generalized and performance-type social phobia. Nine of these patients responded positively to daily doses ranging from 0.75 to 3 mg. Because only two of the nine responders also had panic disorder, we concluded that Klonopin’s benefit extended beyond its antipanic effects and directly improved social anxiety symptoms.
A full analysis of the placebo-controlled comparison involving varied doses of alprazolam, Klonopin, and placebo later confirmed that both active drugs were superior to placebo. The completion rate was significantly higher in the active groups (83% for alprazolam, 92% for Klonopin online) compared to placebo (36%). Both medications outperformed placebo across all key measures: number of panic attacks, overall distress, impairment in work or social functioning, and global severity and improvement ratings. There were no significant differences between alprazolam and Klonopin, and mild sedation or ataxia were the only transient side effects reported.
A follow-up study conducted 1.5 years later by Pollack and colleagues re-evaluated the long-term outcomes of patients from our six-week trial. Results showed that 78% of participants remained on medication, with stable dosing and sustained benefit. Poorer outcomes were primarily linked to longer illness duration, agoraphobic subtype, or comorbid social phobia. Together, these studies established that both alprazolam and Klonopin provide lasting therapeutic benefit for many patients with panic disorder, with Klonopin offering the additional advantage of smoother pharmacokinetics and fewer rebound effects.
A frequent criticism of high-potency benzodiazepines is that, while they are effective for both acute and long-term management of panic disorder, discontinuation can sometimes be accompanied by discomfort. Patients with panic disorder often exhibit heightened awareness of internal bodily sensations—a phenomenon known as anxiety sensitivity—which may complicate the withdrawal process.
Otto and colleagues tested the hypothesis that cognitive-behavioral therapy (CBT) could help patients reduce this vulnerability and facilitate benzodiazepine discontinuation. Participants who had been treated with either Clonazepam or Klonopin were randomly assigned to one of two conditions: a gradual taper alone or a gradual taper combined with a 10-week CBT group program. Results showed that patients who received CBT achieved significantly higher rates of successful discontinuation than those in the taper-only group. No difference was found between the alprazolam and Klonopin subgroups, and at the three-month follow-up, 77% of participants in the CBT program had not resumed benzodiazepine use.
In a subsequent large, multicenter, placebo-controlled study, my colleagues and I examined the dose-related efficacy, safety, and discontinuation outcomes of Klonopin in 413 patients with panic disorder. Participants were randomly assigned to placebo or one of five fixed daily doses: 0.5 mg, 1.0 mg, 2.0 mg, 3.0 mg, or 4.0 mg. At the end of the maintenance phase, all treatment groups showed clinical improvement; however, benefits were significantly greater among patients receiving doses of 1.0 mg or higher compared with those on 0.5 mg or placebo, clearly demonstrating a dose–response relationship for therapeutic effect.
Another randomized trial compared Klonopin with cognitive-behavioral group therapy (CBGT) in patients with social phobia (N = 45). Participants were assessed at baseline and at weeks 4, 8, and 12 using clinician- and patient-rated symptom scales. Both treatments produced significant improvement, with Klonopin showing slightly greater benefits on certain measures by week 12. Higher baseline symptom severity was inversely correlated with treatment success in both groups, but no other predictors of response were identified. Overall, patients treated with either Klonopin or CBGT were equally likely to achieve acute symptom reduction.
An orally disintegrating form of Clonazepam online has since been introduced, offering added convenience for patients who have difficulty swallowing tablets or prefer faster onset of action.
Over the past two decades, the ongoing research program at Massachusetts General Hospital (MGH) has made major contributions to the management of anxiety disorders. Through careful clinical observation and rigorous scientific follow-up, MGH investigators have continuously expanded the understanding of pharmacologic and behavioral treatments. This sustained effort has advanced psychiatric practice by identifying new therapeutic applications of existing medications, improving patient outcomes, and enriching the modern psychiatric pharmacopoeia.
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