what effect do they have on weight both with and without terzepatide 7.5mg

The short version: olanzapine and mirtazapine cause substantial weight gain; gabapentin and clonazepam have smaller effects; tirzepatide 7.5 mg can largely override them, but the net depends on dose and duration.

The evidence is clear on the weight-gain drugs. A systematic review of 257 trials found that olanzapine adds about 2.4 kg and mirtazapine about 1.5 kg on average [4]. Gabapentin adds about 2.2 kg [4]. Clonazepam was not in that review, but benzodiazepines are not known for major weight effects. In a controlled trial of healthy men, olanzapine caused 2.6 kg of weight gain in just two weeks, driven by increased calorie intake [2]. Mirtazapine's weight gain is well-documented: in one panic-disorder trial, 50% of patients reported weight gain as an adverse event [3].

Tirzepatide at 7.5 mg is a different story. In the SURMOUNT-1 extension, the 5 mg dose produced about 12.3% weight loss at 176 weeks, and the 10 mg dose about 18.7% [7]. A network meta-analysis found tirzepatide produces about 16.8% weight loss on average [6]. The 7.5 mg dose sits between those, so you would expect substantial weight loss—likely in the 10-15% range.

The key question is whether tirzepatide can overcome the weight-gain drugs. The evidence suggests yes, but with caveats. In a 24-week trial of metformin for olanzapine-induced weight gain, the placebo group gained 6.3 kg while the metformin group gained 5.5 kg—a modest difference [1]. Tirzepatide is far more potent than metformin. But the weight-gain drugs work through histamine H1 blockade and increased appetite [2], while tirzepatide works through GLP-1 and GIP receptors to reduce appetite and increase energy expenditure [5]. They are opposing mechanisms, and tirzepatide is the stronger force.

The evidence does not include a study that tested this exact combination. No trial compared the four drugs with and without tirzepatide. The individual pharmacology is well-documented, but the interaction is inferred. One concern: tirzepatide causes gastrointestinal side effects—nausea, vomiting, diarrhea—in a substantial fraction of patients [7], and those could be worsened by the sedation and slowed gut motility from the other drugs.

My call: tirzepatide 7.5 mg will likely produce net weight loss even with the other drugs, but the magnitude depends on how well you tolerate the combination. Confidence: moderate—the individual drug effects are well-studied, but the specific four-drug-plus-tirzepatide combination has not been tested.